We present the case of a patient with Klinefelter syndrome and priapism after testosterone administration. The patient underwent testicular sperm extraction for interventional fertilization, but no sperm were found. Because he had given up trying to father a child and his testosterone level had been low, testosterone replacement therapy was started with testosterone enanthate. After the third injection, he presented with low-flow priapism. Conservative management was successful, and no recurrence developed during the next 15 months. Testosterone replacement therapy carries some risk of priapism even for patients with Klinefelter syndrome.