Prolonged suppressive antibiotic therapy may be an alternative to removal of infected orthopedic prostheses in some patients. However, the efficacy of prolonged suppressive antibiotics is not well established. We retrospectively reviewed 18 patients with infected orthopedic prostheses who had been treated with prolonged antimicrobial suppression during the last 10 years. Eighteen episodes of infection were identified in these 18 patients. There were nine men and nine women, and the mean age was 66 years (range, 31-83 years). All patients had a functional prosthesis and were treated with surgical debridement, retention of the prosthesis, and administration of intravenous antibiotics for 6-8 weeks, followed by prolonged oral antibiotic suppression. Fifteen of the 18 patients appear to have had a good response and have been able to retain a functional prosthesis. Complications related to antibiotic suppression occurred in 22% but did not necessitate discontinuation of the antibiotic therapy. Prolonged antibiotic suppression is a reasonable alternative to surgery in selected patients with infected orthopedic prostheses.