The benefit of tadalafil should be justified by its safety and tolerance in the chronic treatment of erectile dysfunction (ED) in general and high-risk population. The main treatment-emergent adverse events, chiefly induced by the interactions of tadalafil with PDE5 and isoforms, are mild or moderate in severity, transient and reversible, which may disappear without drug withdrawal. Tadalafil does not add to the risk and severity of cardiovascular problems, and can be safely co-administered with antihypertensives and selective a-receptor blockers.