OBJECTIVES Two-thirds of patients with Chronic Kidney Disease (CKD) will die of cardiovascular disease (CVD). In addition, 30 year old dialysis patients have a 500-fold increased mortality risk vs. an age-matched general population. Coronary artery calcification (CAC) is a major risk factor for CVD in CKD patients. Increased serum calcium accelerates this process, which suggests that calcium-based phosphate binders (CBBs) may accelerate CAC and increase mortality. The aim of this systematic review was to determine the effect of CBBs vs. non-CBBs on all-cause mortality and CAC among patients with CKD. METHODS We conducted a detailed search of several electronic databases (e.g., MEDLINE, EMBASE, CINHAL) using the following terms: kidney disease, phosphate binders, calcium dialysis, phosphate levels, CV events and mortality. Standard Cochrane methods for study selection and data abstraction were followed. We included nine studies which compared CBBs to non-CBBs. RESULTS Fifty-seven articles were retrieved for detailed evaluation. Sevelamer was the only non-CBB noted in the nine trials which met the inclusion criteria. Sevelamer was associated with a trend towards reduction in all-cause mortality (RR 0.81; 95% CI 0.65-1.02), p=0.07 vs. CBBs. Overall difference in change of CAC scores among those taking sevelamer vs. CBBs was -76.35 (95% CI -158.25 – 5.55), p=0.07. CONCLUSIONS Compared to CBBs, sevelamer is associated with a non-significant trend toward reduced all-cause mortality. This is concordant with the trend toward a modest reduction in CAC progression with sevelamer. Since CBBs are used frequently in CKD patients, this systematic review highlights the need to further evaluate the safety of CBBs in this high-risk population.