Quick answer: All four are PDE5 inhibitors working through the same mechanism, but they differ meaningfully in onset speed, duration, and how much food affects them. Avanafil is fastest to onset (as little as 15 minutes). Tadalafil lasts longest (up to 36 hours) and is least affected by food. Sildenafil and vardenafil sit in the middle on both counts, with vardenafil more sensitive to high-fat meals than sildenafil.
| Sildenafil | Tadalafil | Vardenafil | Avanafil | |
|---|---|---|---|---|
| Brand name | Viagra | Cialis | Levitra | Stendra |
| FDA-approved | 1998 | 2003 | 2003 | 2012 |
| Onset | 30–60 min | 30–45 min | 25–60 min | 15–30 min |
| Duration | 4–6 hours | Up to 36 hours | 4–5 hours | 4–6 hours |
| Food interaction | High-fat meals delay/reduce absorption | Minimal impact | High-fat meals reduce effectiveness 20–30% | Moderate |
| Other approved use | Pulmonary hypertension (as Revatio) | BPH | — | — |
Sildenafil: The Original, Most Studied
Sildenafil was the first PDE5 inhibitor approved, in 1998, and remains the most extensively studied. It works within 30–60 minutes and lasts 4–6 hours. A significant downside: a high-fat meal beforehand meaningfully delays and reduces absorption — timing around food matters more with sildenafil than with tadalafil.
Tadalafil: The Longest Window
Tadalafil's defining feature is duration — effects can last up to 36 hours, earning it the informal "weekend pill" nickname. It's also minimally affected by food, and is the only one of the four with an additional FDA-approved use for benign prostatic hyperplasia (BPH). It's available both as-needed and as a daily low-dose option.
Vardenafil: Similar to Sildenafil, More Selective
Vardenafil works on a similar timeline to sildenafil but is more potent milligram-for-milligram, meaning effective doses are lower. It has higher PDE5 selectivity, which may mean slightly fewer off-target effects for some men, though it carries a caution around QTc interval prolongation for men on certain antiarrhythmic medications. Food interaction is more pronounced than sildenafil — a heavy meal can reduce effectiveness by 20–30%.
Avanafil: The Newest, Fastest Onset
Approved in 2012, avanafil is the newest of the four and is positioned around speed — some men report effects within 15 minutes, the fastest of the group. Duration is similar to sildenafil and vardenafil (4–6 hours), shorter than tadalafil.
Which Providers on This Page Use Which
Most providers here build around sildenafil and tadalafil specifically, sometimes combined with vardenafil in multi-ingredient compounded formulas (Rodeo, Super Strut, FeelGood's QUAD® all include vardenafil alongside other PDE5 inhibitors). Avanafil is less commonly featured across this page's lineup.
It Often Takes More Than One Try
Clinical guidance generally suggests 4–6 attempts before concluding a specific PDE5 inhibitor isn't working for you — individual response varies meaningfully between the four options, and switching between them (with your clinician's guidance) is a normal part of finding what works.
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View MyDrHankPaid LinkIf timing flexibility matters most, tadalafil's 36-hour window is hard to beat. If speed matters most, avanafil is the fastest. If you're food-sensitive, avoid vardenafil around heavy meals specifically. All four have comparable efficacy and safety profiles — the right one is often a matter of fit, tried with your prescriber's guidance.