Musculoskeletal complaints have been reported to occur in as many as 44% of patients with infective endocarditis (IE). A 4-year retrospective review of 104 cases of IE in which new diagnostic criteria were used showed that 24 episodes (23%) began with musculoskeletal complaints. Sixteen of the 24 episodes (66%) involved osteoarticular infection (OAI) documented during the period of hospitalization. Thus, in 15% of the 104 cases of IE, OAI was documented. The 16 episodes occurred in 15 patients, all of whom were intravenous drug abusers (IVDAs). In contrast, OAI was documented in none of the 38 cases in the IE population that did not involve IVDAs. Only three episodes were associated with single rather than multiple bone or joint involvement. There were no deaths, and the patients' conditions seemed to respond well to appropriate therapy. OAIs appear to be uncommon in patients with IE who are not IVDAs. Musculoskeletal complaints in the IVDA population with IE, however, should prompt a careful search for OAI.