Phosphate binders are an important therapeutic option for managing hyperphosphatemia in hemodialysis patients. Whether sevelamer confers a survival advantage over calcium acetate is unclear. Observational cohort study using US Renal Data System (USRDS) data linked to Medicare Part D prescription drug data. Medicare-enrolled elderly incident hemodialysis patients initiating calcium acetate or sevelamer therapy between July 1, 2006, and March 31,2011. Prescription for sevelamer (hydrochloride or carbonate) or calcium acetate. All-cause and cardiovascular-related mortality, hospital admissions and hospital days assessed from Medicare Parts A, B, and D claims and other USRDS data. The sevelamer and calcium-acetate groups included 16,916 and 18,335 patients, respectively. After multivariable adjustment, all-cause (21.9 vs 21.8 deaths/100 patient-years; adjusted HR, 0.97; 95% CI, 0.94-1.03) and cardiovascular (8.7 vs 8.6 deaths/100 patient-years; HR, 0.99; 95% CI, 0.93-1.04) mortality did not differ significantly between the sevelamer and calcium-acetate (referent) groups. Mortality results in propensity score-matched cohorts showed significantly lower risk of death in sevelamer- than in calcium-acetate-treated patients (HR, 0.94; 95% CI, 0.91-0.98). Mortality results from additional analyses including only patients with low-income subsidy status were consistent with results from analyses including patients with and without low-income subsidy status. There were no significant differences between the sevelamer and calcium-acetate groups for all-cause and cardiovascular-related first hospitalization, multiple hospitalizations, and hospital days. Results may not be applicable to younger patients; information about laboratory data and over-the-counter calcium-containing binders was lacking. Relative to treatment with calcium acetate, treatment with sevelamer was associated with similar or slightly lower risk of death and similar risk of hospitalization in elderly incident hemodialysis patients.