The incidence of infective endocarditis in drug addicts is increasing with the spread of intravenous drug abuse. The tricuspid valve is involved most commonly, followed by the mitral. We evaluated 22 patients prospectively with a mean age of 23 years, presenting with addiction-associated endocarditis and referred to our institution during a three-year period. The tricuspid valve was involved in 13 instances, the mitral in four, mitral plus tricuspid valves in five patients and the aortic valve in one. Staphylococcus aureus was the most frequent infective organism (15 cases), followed by streptococci (4 cases), corynebacteria (2 cases) and one case with a mixed infection. Six patients were HIV positive and 17 had evidence of chronic viral hepatitis. Ten patients (three of them HIV positive) were treated surgically. Resection of the tricuspid valve with (one case) or without replacement (four cases), resection of vegetations and tricuspid repair (two cases), mitral valve replacement (2 cases) and aortic valve replacement (one case) were performed. Operative mortality (< 30 days) was high (2/10, 20%); one patient died from cerebral hemorrhage and another from multi-organ failure. Another three patients died after a mean follow up of 10 months. In 12 patients, surgery was not attempted because of still existing intravenous drug abuse or renal and liver failure. Five of these patients died after a mean follow up of 13 months, two from septicemia, two from AIDS-related complications and one from drug overdose. The prognosis of drug-associated endocarditis treated with antibiotics is generally good.(ABSTRACT TRUNCATED AT 250 WORDS)