Introduction. Infective endocarditis (IE) is a severe cardiovascular disorder involving native valves, ventricular or atrial endocardium, foreign intracardiac bodies (prosthetic valves, pacemaker or intracardiac defibrillator), and extracardiac (neurological, nephrological, musculoskeletal system etc.) complications with high mortality and poor prognosis. The objectives of the study were to evaluate clinical and laboratory features of infective endocarditis with musculoskeletal manifestations. Methods. The study was conducted on a sample of 235 patients, 185 being hospitalized in specialized Cardiology Departments, including four medical centers, between November 2014 and March 2016. All patients included in the study fulfilled the diagnostic criteria for infective endocarditis developed after Duke Endocarditis Service (Durham, North Carolina), revised in 1994 and 2007. Results. According to the presence or absence of musculoskeletal manifestations (MSM), patients were divided in 2 groups: 1st group - 90 patients with IE and MSM (38%) and 2nd group - 145 patients with IE without MSM (72%). In this way we found that women develop musculoskeletal symptoms more frequently than men - 44% vs. 36%, although MS symptoms were found in 38% of study patients. The highest incidence of IE in the general study group was seen in men - 70% vs. women - 30% respectively (p = 0.022). Conclusions. From all predisposing cardiac factors in IE patients with MSM the most prevalent ones were: rheumatic valvular heart disease (33%) and valvular prostheses (24%), the predominant bacteremia source being the respiratory infections (52%), poor dental hygiene (33%) and tonsillitis (24%) occurring in patients with diabetes mellitus (23%) and hepatitis (21%).