Only when there is sexual arousal or stimulation does avanafil work. It doesn't result in an erection on its own. Nitric oxide (NO) is released in the penis as a result of sexual excitement. A signaling chemical called nitric oxide causes the blood arteries of the penis to relax. Cyclic guanidine monophosphate (cGMP), which relaxes smooth muscle and widens blood vessels, is produced in response to nitric oxide stimulation.

The phosphodiesterase type 5 (PDE5) enzyme normally breaks down cGMP, which might shorten the length of an erection. PDE5 is specifically inhibited by avanafil, raising cGMP levels in the process.