In 72 drug abusers surgically treated for acute infective endocarditis, 14 patients (19%) required surgical procedures on two valves. The predominant infecting organisms were Staphylococcus aureus and Pseudomonas aeruginosa (29%). In contrast to single valve infection, congestive heart failure was the most common operative indication (86%, p less than 0.05) and was uniformly present when both left-sided valves were involved. Surgery was performed 20 +/- 13 days after initiation of antibiotic therapy, yet 7 of the 14 patients had perivalvular abscess formation. In nine patients with solely left-sided infection, aortic and mitral valve replacements were performed. In five patients with bilateral infection, partial or complete tricuspid valvectomy was performed in conjunction with one aortic and four mitral valve replacements. Tricuspid valve competence was reestablished by valve insertion or anuloplasty in two patients, and these patients experienced less perioperative heart failure than did those with tricuspid excision alone. There was no early (less than 30 day) mortality. However, long-term follow-up revealed a reoperative incidence of 21% and a 36% late mortality rate due to prosthetic valve infection with or without dehiscence at 3 to 18 months (mean 7.2 +/- 6) after the initial operation. These late infectious complications were not related to infecting organism or prosthetic material in the tricuspid anulus, but did occur in four (57%) of seven patients with intracardiac abscess. The data indicate that multiple valve infection does not preclude successful early surgical therapy, maintaining tricuspid competence may be hemodynamically preferable, and reinfection in this addict population increases late mortality.