Coagulase-negative staphylococci are the most frequently isolated microorganisms in early prosthetic valve endocarditis. However, they rarely cause endocarditis in native valves. The profile of patients with left-sided native valve endocarditis by coagulase-negative staphylococci is unknown, because available data are scarce and outdated. We analyzed the epidemiological, clinical, radiographic, microbiological, and echocardiographic features and clinical course in 17 patients with this entity out of a total of 441 consecutive patients diagnosed as having endocarditis. The results show that left-sided native valve endocarditis caused by coagulase-negative staphylococci is more common than previously reported, can cause heart failure due to valvular involvement, often needs surgery, and is associated with high mortality.