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Background: The appropriate prescription of dialysate calcium concentration for hemodialysis is debated. We investigated the association between dialysate calcium and all-cause, cardiovascular mortality and sudden cardiac death., Methods: In this historical cohort study, we included adult incident hemodialysis patients who initiated dialysis between 1 January 2010 and 30 June 2017 who survived for at least 6 months (grace period). We evaluated the association between dialysate calcium 1.25 or 1.50 mmol/l and outcomes in the 2 years after the grace period, using multivariable Cox regression models. Moreover, we examined the association between the serum dialysate to calcium gradient and outcomes., Results: We included 12 897 patients with dialysate calcium 1.25 mmol/l and 26 989 patients with dialysate calcium 1.50 mmol/l. The median age was 65 years, and 61% were male. The unadjusted risk of all-cause mortality was higher for dialysate calcium 1.50 mmol/l [hazard ratio (HR) 1.07, 95% confidence intervals (CI) 1.01-1.12]. However, in the fully adjusted model, no significant differences were noted (HR 1.05, 95% CI 0.99-1.12). Similar results were observed for the risk of cardiovascular mortality (HR 1.03, 95% CI 0.94-1.13). Adjusted risk of sudden cardiac death was lower for dialysate calcium 1.50 mmol/l (HR 0.81, 95% CI 0.67-0.97). Significant and positive associations with all outcomes were observed with larger serum-to-dialysate calcium gradients, primarily mediated by the serum calcium level., Conclusions: In contrast to the unadjusted analysis that showed a higher risk for dialysate calcium of 1.50 mmol/l, after adjusting for confounders, there were no significant differences in the risk of all-cause and cardiovascular mortality between dialysate calcium concentrations of 1.50 and 1.25 mmol/l. After adjustment, a lower risk of sudden cardiac death was observed in patients with dialysate calcium 1.50 mmol/l. A higher serum-to-dialysate calcium gradient is associated with an increased risk for adverse outcomes., Competing Interests: The data were extracted from EuCliD®, which is managed by Fresenius Medical Care (FME). P.C., F.B., S.S., and L.N. are employees at FMC. S.S. holds stocks from FMC. K.t.Me., H.B., and J.K. received a speaker's fee from FMC. J.K. also received a speaker's fee from Baxter Healthcare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)