A man with stenosis of the aortic valve acquired endocarditis after abdominal surgery. Klebsiella pneumoniae and Acinetobacter calcoaceticus were cultured from his blood. The blood cultures remained positive despite intravenous gentamicin and cephalothin to which the organisms were sensitive in vitro. Ultimately, the blood was sterilized by a combination of gentamicin and trimethoprim-sulfamethoxazole taken orally. The course of the patient was complicated by cardiac arrest and pericardial tamponade caused by a valve ring abscess and a dissecting mycotic aneurysm of the coronary sinus of Valsalva. Aortic valve replacement and right coronary artery bypass were performed. A prolonged course of trimethoprim-sulfamethoxazole was given postoperatively, and the patient has had no evidence of recurrent infection after five years. Trimethoprim-sulfamethoxazole, in combination with other antibiotics, has been successfully used to treat other patients with bacterial endocarditis and thus may be an alternative for patients in whom conventional therapy has failed.