A retrospective study compared the effects of dialysate calcium concentrations of 1.25 mmol/L (DCa 1.25) and 1.5 mmol/L (DCa 1.5) on blood pressure variability during hemodialysis in 711 patients at two Chinese centers. 2061 hemodialysis sessions were analyzed, with 473 patients (1425 sessions) having a DCa of 1.25 and 238 patients (636 sessions) having a DCa of 1.5. Systolic blood pressure variability (SBPV) was 1.25 lower in the DCa group (25.23 ± 14.55 mmHg versus 32.42 ± 17.71 mmHg, p < 0.001). Diastolic blood pressure variability was 8.07 ± 8.07 mmHg versus 11.56 ± 9.67 mmHg (p < 0.001) and mean arterial pressure variability (MAPV) 15.41 ± 9.40 mmHg versus 18.71 ± 11.10 mmHg (p < 0.001). Changes in total serum calcium were smaller at DCa 1.25 [0.04 (-0.06, 0.16) mmol/L vs 0.15 (0.04, 0.26) mmol/L, p < 0.001] and positively correlated with SBPV and MAPV. In multivariate models, a DCa of 1.5 was independently associated with higher blood pressure variability. Lower dialysate calcium concentration minimizes calcium flux and improves hemodynamic stability.