In many cardiovascular and infectious diseases, there are clinical and prognostic differences between men and women. The aim of this study was to compare the presentation of left-sided infective endocarditis in the two sexes. A total of 621 episodes of left-sided infective endocarditis (395 in men, 226 in women) were studied. The comparative analysis considered epidemiological, clinical, microbiological, echocardiographic and prognostic variables. Despite marked epidemiological, echocardiographic and microbiological differences between men and women, clinical characteristics, treatment approaches and outcomes (in-hospital mortality: 28% in men and 35% in women; P = .1) were similar in our patient series.