This is a longitudinal study on 53,560 hemodialysis patients from the Japan Renal Data Registry. Predictor was D[Ca] ≥3.0 vs 2.5 mEq/L. Outcomes were the first CV events during 1-year observation period. Association of D[Ca] with CV events and effect modifications were tested using multivariate logistic regression analyses. Diabetes mellitus (DM) was a significant effect modifier for association of higher D[Ca] and myocardial infarction (MI) (OR: 1.26 (1.03-1.55) among DM and 0.86 (0.72-1.03) among non-DM, p for interaction <0.01). The effect size was not affected by further adjustment for serum albumin-corrected Ca or intact parathyroid hormone (iPTH) levels, but was attenuated by adjustment for intradialytic change in serum Ca concentration (ΔCa) (1.16 [0.89-1.51]). Among DM, D[Ca] ≥3.0 mEq/L was significantly associated with MI in the first tertile of corrected Ca or iPTH ≤60 pg/ml (p for interaction 0.03 and 0.03, respectively). In conclusion, higher D[Ca] was associated with incident MI in DM, especially with low serum Ca or iPTH levels. Attenuation of the effect size by adjustment for ΔCa and stratified analyses suggest that larger Ca influx during dialysis with higher D[Ca] in patients suggestive of low bone turnover leads to vascular calcification and subsequent MI in DM.