Guidelines restricting use of calcium-based phosphate binders in all patients with end-stage renal disease owing to their potential contribution to increased cardiovascular risk shifted prescribing from calcium acetate toward the costlier sevelamer carbonate products.; To compare cardiovascular events and mortality between patients with end-stage renal disease (ESRD) undergoing hemodialysis receiving sevelamer vs calcium acetate in real-world practice.; An observational cohort study was conducted using the United States Renal Data System linked to Medicare claims data (May 1, 2012, to December 31, 2013). Data analysis was performed from October 2017 to September 2018. Participants included patients 65 years or older with ESRD within 180 days after starting hemodialysis (sevelamer, 2647; calcium acetate, 2074).; New use of sevelamer (calcium-free phosphate binder) vs calcium acetate (calcium-based phosphate binder).; Hazard ratios (HRs) with 95% CIs were estimated for fatal or nonfatal cardiovascular events (myocardial infarction or ischemic stroke: primary outcome) and all-cause mortality (secondary outcome) using Cox proportional hazards regression with fine stratification on the propensity score to control for potential confounders, including phosphorus and calcium levels.; After propensity score weighting, 2639 patients initiating sevelamer treatment (1184 men [44.9%]; mean [SD] age, 75.6 [6.9] years) and 2065 patients initiating calcium acetate treatment (930 men [45.0%]; mean [SD] age, 75.5 [7.1] years) were included in the analysis. Crude incidence rates (IRs) for cardiovascular events of 458 per 1000 person-years for sevelamer and 464 per 1000 person-years for calcium acetate were observed. After propensity score fine-stratification weighting, HRs of 0.96 (95% CI, 0.84-1.10) for cardiovascular events were observed. Results were consistent within subgroups of age (<75 y: primary outcome, HR, 1.02; 95% CI, 0.85-1.24; vs ≥75 years: primary outcome, HR, 0.83; 95% CI, 0.69-1.01) and sex (primary outcome in men: HR, 1.02; 95% CI, 0.83-1.26).; The results of the study do not suggest increased cardiovascular safety of sevelamer in the routine clinical practice of patients with ESRD compared with calcium acetate; this study's findings suggest that well-designed, long-term, randomized clinical trials are needed.