The HACEK group of fastidious gram-negative organisms is a recognized but unusual cause of infective endocarditis, responsible for approximately 3% of cases. We report our experience with 45 cases of endocarditis caused by HACEK organisms. In Olmsted County, Minnesota, the incidence of HACEK endocarditis was 0.14 per 100,000 person-years. In patients with native valves, 33 cases occurred, and in patients with prosthetic valves, 12 cases occurred. The most common presenting symptoms were fever, splenomegaly, new or changing murmur, and microvascular phenomena. Symptoms were present in the majority of patients anywhere from two weeks to six months prior to diagnosis. Blood cultures became positive in a mean 3.375 days, and therapy with a beta-lactam alone or as part of a combination was given for anywhere between three and six weeks. Within the first month of diagnosis, surgery was performed for 13 regurgitant valves in 11 patients (24%). Echocardiography was an insensitive predictor of subsequent major arterial embolization (odds ratio, 1.33; 95% confidence interval, 0.31-5.67). The overall survival in our cohort of patients was 87%. These results confirm previous reports that HACEK endocarditis portends a favorable prognosis.