A healthy 46-year-old man presented to the Emergency Department with a 36-hour history of persistent, painful erection after taking the cyclic guanylyl monophosphate-specific phosphodiesterase 5 inhibitor tadalafil. He had no other identified contributing factors for priapism. After confirmation of ischemic priapism and failure of bedside management in the Emergency Department, the patient underwent operative caverno-spongiosal shunting. Postoperatively, the erection initially rebounded but gradually receded with manual compression over 48 hours. At outpatient follow-up, the patient remained flaccid without erections. To our knowledge, this is the first report of tadalafil-associated priapism.