BACKGROUND : Little is known about the current clinical profile and outcomes of patients with infective endocarditis (IE) in South Africa (SA). OBJECTIVE : To provide a contemporary and descriptive overview of IE in a representative SA tertiary centre. METHODS : We conducted a retrospective review of the records of patients admitted to Groote Schuur Hospital, Cape Town, between 2009 and 2016 fulfilling universal criteria for definite or possible IE, in search of demographic, clinical, microbiological, echocardiographic, treatment and outcome information. RESULTS : A total of 105 patients fulfilled the modified Duke criteria for IE. The median age of the cohort was 39 years (interquartile range (IQR) 29 - 51), with a male preponderance (61.9%). The majority of the patients (72.4%) had left-sided native valve endocarditis, 14.3% had right-sided disease, and 13.3% had prosthetic valve endocarditis. A third of the cohort had rheumatic heart disease. Although 41.1% of patients with left-sided disease had negative blood cultures, the three most common organisms cultured in this subgroup were Staphylococcus aureus (18.9%), Streptococcus spp. (16.7%) and Enterococcus spp. (6.7%). Participants with right-sided endocarditis were younger (29 years, IQR 27 - 37) and were mainly intravenous drug users (73.3%), and the majority cultured positive for S. aureus (73.3%) with frequent septic pulmonary complications (40.0%). The overall in-hospital mortality was 16.2%, with no deaths in the group with right-sided endocarditis. Predictors of death in our patients were heart failure (odds ratio (OR) 8.16, 95% confidence interval (CI) 1.77 - 37.70; p=0.007) and age >45 years (OR 4.73, 95% CI 1.11 - 20.14; p=0.036). Valve surgery was associated with a reduction in mortality (OR 0.09, 95% CI 0.02 - 0.43; p=0.001). CONCLUSIONS : IE remains an important clinical problem in a typical teaching tertiary care centre in SA. In this setting, it continues to affect mainly young people with post-inflammatory valve disease and congenital heart disease. The in-hospital mortality associated with IE remains high. Intravenous drug-associated endocarditis caused by S. aureus is an important IE subset, comprising ~10% of all cases, which was not reported 15 years ago, and culture-negative endocarditis remains highly prevalent. Heart failure in IE carries a significant risk of death and needs a more intensive level of care in hospital. Finally, cardiac surgery was associated with reduced mortality, with the largest impact in patients with heart failure.