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RATIONALE Adult sepsis survivors have an increased risk of experiencing long-term cardiovascular events. OBJECTIVE To determine whether the cardiovascular risk following sepsis is mitigated by renin-angiotensin system inhibitors (RASi). METHODS Population-based cohort study of adult sepsis survivors designed to emulate a target randomized trial with an active comparator and new-user design. We excluded patients with a first-line indication for prescription of RASi (e.g., coronary heart disease, heart failure, chronic kidney disease, and hypertension with diabetes mellitus). The main exposure of interest was a new prescription of a RASi within 30 days of hospital discharge. The active comparator was a new prescription of either a calcium channel blocker or a thiazide diuretic, also within 30 days of hospital discharge. The primary outcome of interest was the composite of myocardial infarction, stroke, and all-cause mortality during follow-up to 5 years. We used inverse probability weighting of a Cox proportional hazards model and reported results using hazards ratios (HR) with 95% confidence intervals (CI). RESULTS The cohort included 7,174 adult sepsis survivors, of whom 3,805 were new users of a RASi and 3,369 were new users of a calcium channel blocker or a thiazide diuretic. New users of a RASi experienced a lower hazard of major cardiovascular events compared to new users of a calcium channel blocker or a thiazide diuretic (HR 0.93, 95% CI 0.87 - 0.99). This association was consistent across different follow-up intervals and multiple sensitivity analyses. CONCLUSION A new RASi prescription is associated with a reduction in major cardiovascular events after sepsis. A randomized controlled trial should be considered to confirm this finding.