The prognostic value of the sequential organ failure assessment (SOFA) score for critically ill elderly patients with acute infective endocarditis (IE) remains unknown. From January 2015 to December 2019, 111 elderly (≥65 years) patients with acute IE were consecutively included and divided into a low SOFA (<6) group (n = 71) and a high SOFA (≥6) group (n = 40). Endpoints included in-hospital and long-term (12-36 month) mortality. A high SOFA score was related to higher incidence of in-hospital mortality (30.0%) with an area under the curve (AUC) of 0.796. In multivariate analysis, age [odds ratio (OR) = 2.21, 95% confidence intervals (CI), 1.16-6.79, p = 0.040], SOFA ≥6 (OR = 6.38, 95% CI, 1.80-16.89, p = 0.004) and surgical treatment (OR = 0.21, 95% CI, 0.05-0.80, p = 0.021) were predictive of in-hospital mortality. A Cox proportional-hazards model identified age [Hazard ratios (HR)= 2.85, 95% CI, 1.11-7.37, p = 0.031], diabetes mellitus (HR = 3.99, 95% CI, 1.35-11.80, p = 0.013), SOFA ≥6 (OR = 3.38, 95% CI, 1.26-9.08, p = 0.001) and surgical treatment (HR = 0.24, 95% CI, 0.08-0.68, p = 0.021) as predictors of long-term mortality. A high SOFA score predicts a poor outcome including in-hospital and long-term mortality in critically ill elderly patients with acute IE., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)