Aim: To describe the changes observed in operated patients with infective endocarditis (IE) in the south-central region of Chile during the last four decades. Methods: Case series study. The target population was patients diagnosed with IE and indication for valve surgery between 1983 and 2020 from a Chilean public hospital. The universe (n = 306) was divided into four groups according to the period of valve surgery. Sociodemographic and clinical variables between these groups were compared using the Kruskal-Wallis and Chi-square tests for independence. Cumulative survivals were calculated and compared using the Gehan-Breslow-Wilcoxon test. Results: Age at diagnosis (p < 0.001), frequency of comorbidities (p < 0.001), clinical presentation compatible with acute kidney injury (p < 0.001), independent mitral valve involvement (p < 0.001), positivity of microbiological cultures (p < 0.012) and cumulative survival (p = 0,015) increased. The delay from symptom onset to diagnosis (p = 0.003), clinical presentation compatible with heart failure (p < 0.001), independent involvement of the aortic valve (p < 0.001), and surgical indication for large vegetation (p < 0.001) decreased. Conclusions: The IE profile of patients seen in a public hospital in the south-central region of Chile has undergone significant changes during the last four decades.