Priapism is a complication of sickle cell disease, and for those with severe prolonged attacks, it is serious, often resulting in permanent sexual impairment. Treatment is frustating, and psychological consequences may be profound. A 20-year-old sickle cell patient with intractable priapism associated with intense pain and penile gigantism underwent multiple but unsuccessful medical and surgical treatment regimens. Finally, corpora cavernosa corporectomy was performed. The pathologic findings of extensive vascular thrombosis and stromal fibrosis underscore the irreversibility of this process and explain the inevitable impotence. Pain and sexual impairment were associated with serious psychological difficulties and suicide attempts. Counseling and close follow-up have improved his outlook considerably. He has been pain-free for 1 year, and future management includes consideration of placement of a penile prosthesis.