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Infective endocarditis (IE) is a severe pathology with recent changes in its epidemiological profile, characterised by older patients with more comorbidities. The objective of this study is to describe the clinical and microbiological characteristics, as well as potential factors associated with mortality, of patients with IE in a tertiary academic centre. Material and Methods: Descriptive, retrospective, and observational study of patients over 18 years of age with a confirmed diagnosis of IE, conducted between 2021 and 2023 at the Dr Hernán Henríquez Aravena Hospital in Temuco, Chile. Biodemographic variables, risk factors, microbiology, echocardiographic findings, and complications were analysed using descriptive statistics and logistic regression models. Results: 119 patients were included (average age 60 years; 65.5% male; 28.5% rural). The most frequent risk factors were arterial hypertension (55%) and diabetes mellitus (29%). 18% were on haemodialysis (HD). Microbiological isolation was achieved in 78.1% of cases, with Streptococcus gallolyticus the most frequent isolate (16.8%), followed by Staphylococcus aureus (15.1%) and coagulase-negative Staphylococcus (15.1%). Complications were present in 69% of cases, mainly emboli (43%) and septic shock (23%)-59.6% required surgery. Global mortality was 44.5%, with a decreasing annual trend (from 58% in 2021 to 33% in 2023). Comorbidities and complications independently associated with mortality were chronic renal failure on HD (OR 5.76; p = 0.001), heart failure (OR 3.13; p = 0.025), and septic shock (OR 3.31; p = 0.016). Conclusions: IE in this centre presents an aggressive profile and a high burden of comorbidities. The prevalence of S. gallolyticus is a notable regional observation not reported in similar populations. Mortality remains high, with an improving trend.