ED Medication Comparison: Which One Is Right for You?
All four FDA-approved ED medications work through the same mechanism, but they differ in meaningful ways: how fast they work, how long they last, and their side effect profiles. Here's a comprehensive comparison to help you understand your options.
Quick Summary
Since sildenafil (Viagra) was approved in 1998, three additional PDE5 inhibitors have joined it: tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra). All four are effective for erectile dysfunction, with clinical efficacy rates of 60-80%. But the differences between them can matter depending on your lifestyle, preferences, and health profile.
How They All Work
All four medications belong to the same drug class: phosphodiesterase type 5 (PDE5) inhibitors. They work by blocking the enzyme that breaks down cyclic GMP (cGMP), a chemical that causes blood vessel relaxation. With more cGMP available, blood flows more easily into the penis during sexual arousal.
The key point: these medications don't create arousal or desire—they enhance the body's response to sexual stimulation. None will cause an erection without arousal.
Head-to-Head Comparison
| Feature | Sildenafil (Viagra) |
Tadalafil (Cialis) |
Vardenafil (Levitra) |
Avanafil (Stendra) |
|---|---|---|---|---|
| FDA Approved | 1998 | 2003 | 2003 | 2012 |
| Time to onset | 30-60 min | 30-45 min | 30-60 min | 15-30 min |
| Duration | 4-6 hours | Up to 36 hours | 4-6 hours | 6-12 hours |
| Half-life | ~4 hours | ~17.5 hours | ~4-5 hours | ~3-5 hours |
| Standard doses | 25, 50, 100mg | 5, 10, 20mg | 5, 10, 20mg | 50, 100, 200mg |
| Food effect | Yes (fatty meals delay) | Minimal | Yes (fatty meals reduce) | Yes (delays ~1 hour) |
| Daily dosing | No | Yes (2.5-5mg) | No | No |
| Generic available | Yes | Yes | Yes | Yes |
Detailed Breakdown of Each Medication
Sildenafil (Viagra)
Best for:
- • Men who want predictable, on-demand effectiveness
- • Those who prefer the most studied option
- • Budget-conscious patients (cheapest generic)
Consider alternatives if:
- • You want longer spontaneity windows
- • Visual side effects are a concern
- • You often have heavy meals before sex
Sildenafil is the original and most extensively studied ED medication. Clinical trials show improved erections in 77-84% of men. It has the most cross-reactivity with PDE6 (the enzyme in the retina), which is why some men report seeing a blue tint or increased brightness—effects that are temporary and harmless but can be annoying.
Tadalafil (Cialis)
Best for:
- • Men who want spontaneity (the "weekend pill")
- • Those who prefer daily dosing option
- • Men who also have BPH/urinary symptoms
- • Those who don't want to time meals
Consider alternatives if:
- • You have heart conditions requiring nitrates
- • Back pain or muscle aches are concerns
- • You prefer medication to clear quickly
Tadalafil's 17.5-hour half-life (compared to ~4 hours for sildenafil) means effects can last up to 36 hours—hence the "weekend pill" nickname. In preference studies, about 69% of men preferred tadalafil over sildenafil, primarily due to this longer duration. It's also the only PDE5 inhibitor approved for daily use, and it's FDA-approved for both ED and benign prostatic hyperplasia (BPH). The trade-off: if you experience side effects, they may last longer, and the prolonged duration means a longer wait before nitrates could be safely used in an emergency.
Vardenafil (Levitra)
Best for:
- • Men who experienced visual changes on sildenafil
- • Those seeking similar profile to sildenafil with potentially fewer visual effects
Consider alternatives if:
- • You want longer duration
- • You often eat before sex (fat affects absorption)
- • Price is a major concern
Vardenafil is structurally similar to sildenafil but is more biochemically potent (so lower doses are used) and more selective for PDE5. Importantly, it has less cross-reactivity with PDE6, which means it's less likely to cause the visual side effects some men experience with sildenafil. Clinical efficacy is similar to sildenafil. One disadvantage: high-fat meals reduce its absorption more than they affect sildenafil.
Avanafil (Stendra)
Best for:
- • Men who want the fastest onset (15-30 min)
- • Those who experienced side effects on other PDE5 inhibitors
- • Men who want minimal planning required
Consider alternatives if:
- • You want longer duration of effect
- • Cost is a major concern (generic is newer, may be pricier)
- • You prefer medications with longer track records
Avanafil is the newest PDE5 inhibitor and was designed with selectivity in mind. It has the highest selectivity for PDE5 over other PDE subtypes, which theoretically means fewer side effects from cross-reactivity. Clinical data supports this: headache rates with avanafil 200mg were 9.3% compared to 12.8% with sildenafil 100mg, and flushing was 3.7% vs 10.4%. Its fast onset (as quick as 15 minutes) makes it ideal for spontaneity, though its effects don't last as long as tadalafil.
Side Effect Comparison
All PDE5 inhibitors share common side effects because they all work through the same basic mechanism. However, because each medication has slightly different selectivity for other PDE subtypes, their side effect profiles vary:
| Side Effect | Sildenafil | Tadalafil | Vardenafil | Avanafil |
|---|---|---|---|---|
| Headache | ~13% | ~15% | ~16% | ~9% |
| Flushing | ~10% | ~4% | ~11% | ~4% |
| Nasal congestion | ~4% | ~4% | ~10% | ~2% |
| Visual changes | ~5% | ~0.1% | ~2% | Rare |
| Back pain/myalgia | Rare | ~6% | Rare | Rare |
Which Should You Choose?
There's no single "best" ED medication—the right choice depends on your specific situation. Here's a decision framework:
If you want maximum spontaneity:
Consider tadalafil. Its 36-hour window means you can take it on Friday and be ready through Sunday. Daily low-dose tadalafil (2.5-5mg) provides continuous coverage without planning around pills.
If you want the fastest onset:
Consider avanafil. Working in as little as 15 minutes, it requires the least advance planning. Good for situations where timing is uncertain.
If you want the most affordable option:
Consider generic sildenafil or tadalafil. Both have been generic for years and are widely available at low cost. Sildenafil is typically the cheapest.
If you experienced side effects on another PDE5 inhibitor:
Try a different one—they have different selectivity profiles. Avanafil has the lowest reported side effect rates. If visual changes bothered you on sildenafil, vardenafil or tadalafil may be better.
If you also have BPH (enlarged prostate) symptoms:
Consider tadalafil—it's the only PDE5 inhibitor FDA-approved for both ED and BPH. Daily 5mg dosing addresses both conditions.
If you have heart disease or take nitrates:
All PDE5 inhibitors are contraindicated with nitrates. If you might need nitrates for chest pain, shorter-acting options (sildenafil, vardenafil, or avanafil) clear from your system faster than tadalafil—an important consideration for emergency situations.
What If One Doesn't Work?
About 20-40% of men who try a PDE5 inhibitor don't respond adequately or discontinue due to side effects. If your first choice doesn't work well:
- 1. Make sure you're using it correctly: Take it on an empty stomach (except tadalafil), give it enough time to work, and ensure you're sexually aroused. Some men give up too quickly.
- 2. Try a different dose: You may need a higher dose, especially if you have diabetes or other conditions that affect blood flow.
- 3. Try a different medication: Non-response to one PDE5 inhibitor doesn't mean others won't work. Many men find success after switching.
- 4. Address underlying issues: Low testosterone, untreated depression, relationship issues, or poorly controlled diabetes can all reduce PDE5 inhibitor effectiveness.
Important Considerations for All PDE5 Inhibitors
Contraindications (Apply to All)
- • Never combine with nitrates (nitroglycerin, isosorbide) or "poppers" (amyl nitrite)—can cause dangerous blood pressure drops
- • Use caution with alpha-blockers for BPH
- • Avoid if you've had recent stroke or heart attack
- • Tell your doctor about all medications, especially for HIV, fungal infections, or blood pressure
Regardless of which medication you choose, the nitrate interaction is the most critical safety concern. If you have heart disease and use nitroglycerin for chest pain, you must wait at least 24 hours after sildenafil, vardenafil, or avanafil (48 hours for tadalafil) before taking nitrates.
Ready to Find the Right ED Medication?
Online telehealth platforms make it easy to consult with a licensed provider who can help you choose the best option based on your health profile, preferences, and lifestyle.
The Bottom Line
All four FDA-approved ED medications are effective, with efficacy rates of 60-80%. The main differences are duration (tadalafil wins), onset speed (avanafil wins), and side effect profiles (avanafil has the best numbers, but all are generally well-tolerated). Most men start with sildenafil or tadalafil due to cost and familiarity. If one doesn't work or causes bothersome side effects, trying a different option often succeeds.