The epidemiology, and clinical and microbiological spectrum, of infective endocarditis (IE) in Greece was analysed in a prospective 4-year study in a tertiary hospital and a heart surgery centre in Athens. In total, 101 cases of IE (71 men, 30 women, aged 54.4 +/- 17.1 years) were studied, with a follow-up period of 3 months. Seventy-seven cases were definite and 24 possible; 59 involved native valves (native valve endocarditis; NVE), 31 prosthetic valves (prosthetic valve endocarditis; PVE), of which nine were early and 22 late, and 11 permanent pacemakers (pacemaker endocarditis; PME). There was a predominant involvement of aortic (48/101) and mitral (40/101) valves. Seven patients had rheumatic valvular disease, two had mitral valve prolapse, and eight had a previous history of IE. Thirteen and six patients had undergone dental and endoscopic procedures, respectively. In 13 patients, intravenous catheters were used within the 3 months before diagnosis of IE. There were three intravenous drug users among the patients. Staphylococcus aureus was the most important pathogen, isolated in 22% of cases, followed by viridans streptococci (19%) and coagulase-negative staphylococci (16%). Enterococcus spp. were responsible for 3%, HACEK group for 2%, and fungi for 6% of cases. Viridans streptococci were the leading cause of NVE (29%), Staphylococcus epidermidis of PVE (16%), and S. aureus of PME (54.5%). Six of 22 S. aureus and ten of 16 S. epidermidis isolates were methicillin-resistant. Surgical intervention, including total pacemaker removal, was performed in 51.5% of patients. Overall mortality was 16%, but was 29% with PVE, and was significantly higher with medical than with combined surgical and medical therapy (24.5% vs. 8%). Compared with previous studies, there were changing trends in the epidemiology, microbiology, treatment and prognosis of IE in Greece.