Historically, infective endocarditis (IE) in South Africa (SA) was associated with the viridans group of streptococci affecting patients with underlying rheumatic heart disease (RHD). A changing IE bacteriological profile raises the question of whether the profile of underlying valvular abnormality has changed. To investigate the prevalence of underlying structural valve abnormalities and their aetiologies associated with IE in SA, and describe the typical imaging findings. The Tygerberg Endocarditis Cohort study prospectively enrolled patients with IE between November 2019 and April 2021. Patients underwent detailed transthoracic and transoesophageal echocardiography to assess their underlying cardiac and valvular structure. Among 71 patients included, a predisposing endocardial abnormality was detected in 49.3%, with RHD the most common single identifiable aetiology (16.9%). The in-hospital mortality rate was similar in patients with and without a predisposing endocardial abnormality (20% v. 16.7%; p=0.72), as was the rate of embolic events (20% v. 27.2%; p=0.58). Significantly more patients with a predisposing endocardial abnormality had an indication for surgery (94.3% v. 69.4%; p<0.01). The viridans group of streptococci was more prevalent in patients with a predisposing endocardial abnormality (25.7% v. 2.7%; p<0.01). Left-sided linear vegetation size >10 mm was associated with an increased risk of in-hospital mortality (24% v. 5%; p=0.05). We observed a marked decrease in the prevalence of RHD in this cohort of patients with IE. The viridans group of streptococci was an uncommon cause of IE in patients with no predisposing endocardial abnormality detected. The presence of a predisposing endocardial abnormality was not associated with an increased risk of in-hospital mortality or embolic events. Linear vegetation length >10 mm was associated with an increased risk of in-hospital mortality in patients with left-sided IE.