Active infective endocarditis (IE) is a disease of low incidence that has showed changes in presentation, diagnosis and treatment options during the past decades. Despite these advances, mortality remains very high. Our goal was to analyze the characteristics of patients with active IE and their relationship with in-hospital mortality over 16 years. Between 1994 and 2010 we performed a prospective registry of 152 consecutive patients (64.5% male, age 45 ± 16 years) admitted with IE. Clinical characteristics, treatment and inpatient outcomes were analyzed. The most common causes of underlying heart disease were: congenital (21%) and rheumatic fever (13.2%). The reasons for hospitalization were fever (76.3%) and heart failure (40.1%). The infectious agent was identified in 69.7% of cases, and the most frequent was Streptococcus viridans. The echocardiogram showed vegetations in 80.9% of patients and 57.8% of them presented complications (the most frequent was heart failure) during hospitalization. Surgical treatment was indicated in 63.2% of cases, mainly due to heart failure. The overall hospital mortality was 30.2%. The presence of complications, requirement of surgical treatment and refractory heart failure were independent predictors of mortality whereas the single presence of vegetation showed better survival rate. The identification of these predictors could help to improve the outcomes in IE.