Background Epidemiological features of infective endocarditis have changed during the last decades because of increases in the prevalence of health care exposure and of Staphylococcus aureus bloodstream infection. Consequently, the role of surgery is evolving. We aim to provide a contemporary profile of epidemiological, microbiological, and clinical features of infective endocarditis in a tertiary medical center, and identify predictors of mortality. Methods A prospective observational cohort study of consecutive adult patients with definite endocarditis according to the modified Duke criteria. Data were collected from January 1, 2009 through October 31, 2011 following a predefined case report form designed by the ICE-PCS. Results Among 70 endocarditis episodes, 25.7% involved prosthetic valves and 11.5% were device related. Forty-four percent of episodes were health-care associated. The predominant causative microorganism on native valve, prosthetic valve and device related endocarditis was Staphylococcus aureus (33.3%). Viridans group streptococci accounted for the majority of community-acquired endocarditis (36.1%). At least one complication occurred in 50% of the episodes. One third of the patients who had an indication for surgery were operated upon. Six month case fatality ratio was 40%. Sixty-five percent of patients with a contraindication to surgery died, compared with 9% and 28.5% who were treated surgically and medically, respectively. In multivariable analysis, age was a predictor of mortality. Conclusion Compared with other series, we observed more health-care associated endocarditis, and a higher mortality. Nearly half of all deaths were in patients who had a contraindication to surgery. Careful evaluation of contraindications to surgery is warranted.