In a retrospective study, the effect of long-term treatment with sulfamethoxazole-trimethoprim was evaluated in nine male patients with chronic granulomatous disease. During this treatment, a marked reduction was observed in the number of infectious episodes, the number of causative agents, and the number of surgical interventions. Furthermore, a significant reduction in days of hospitalization per year was found. The mean observation period was six years before and four years during treatment. Transient alopecia was observed in one patient during therapy. We conclude that prophylactic treatment with sulfamethoxazole-trimethoprim is beneficial in patients with chronic granulomatous disease.