Tadalafil is at least 9000 times more selective for PDE5 than most of the other families of PDEs, with the exception of PDE11. PDE11 is found in the testes and prostate; however, despite partial inhibition of PDE11 by tadalafil at therapeutic doses, clinical significance of this observation has yet to be fully understood. A study by Hellstrom and colleagues concluded that there are no harmful effects of tadalafil on spermatogenesis or testicular function.

The PDE enzyme responsible for phototransduction in the retina, PDE6, is inhibited to some degree by canadian sildenafil and canadian vardenafil, but not canadian tadalafil. The inhibition of PDE6 explains the side effect of blue vision experienced by some patients with these two drugs, as PDE6 inhibition in the retina causes impairment of blue-green color discrimination. Slightly less common with vardenafil, altered vision is a reported side effect for 11% of men taking sildenafil 100 mg. Compared with sildenafil and vardenafil, tadalafil is much less inhibitory for PDE6, and it is over 700 times more potent for PDE5 than PDE6. For this reason, generic tadalafil has less than 0.1% occurrence of vision abnormalities.