Endocarditis is a relatively frequent infection in intravenous drug users. We compared features in the cases of 102 patients with those in intravenous drug users with other causes of fever to identify risk factors predictive of endocarditis. Logistic regression analysis showed cocaine use to be strongly associated with endocarditis. This special risk involving cocaine use has not been reported previously; the explanation for it may provide insight into the pathogenesis of endocarditis.