Tadalafil is an inhibitor of phosphodiesterase 5, approved for the treatment of erectile dysfunction. Blood pressure-lowering effects of tadalafil in healthy volunteers are minimal. In patients on a broad spectrum of antihypertensive medication, severe hypotension did not occur in combination with tadalafil; however, a combination of tadalafil with any nitric oxide donor can lead to life-threatening hypotension and is, therefore, absolutely contraindicated (at least 48 h interval after last dose of tadalafil). Combination with alpha-blocking agents, such as doxazosin, may only be considered when patients are hemodynamically stable for a longer period using the lowest dose of tadalafil and with close blood pressure monitoring. In placebo-controlled trials, severe adverse cardiovascular events were rare in tadalafil users and similar in frequency in comparison to placebo. However, as cardiovascular disease is highly prevalent in patients with erectile dysfunction, a complete diagnostic work up of these patients and potentially optimized cardiovascular treatment may be necessary before sexual intercourse can be recommended and tadalafil may be prescribed.