Background and objectives Serum calcification propensity is a novel functional test that quantifies the functionality of the humeral system of calcification control. Serum calcification propensity is measured by T ₅₀ , the time taken to convert from primary to secondary calciprotein particle in the serum. Lower T ₅₀ represents higher calcification propensity and is associated with higher risk of cardiovascular events and death in patients with ESKD. Increasing magnesium in serum increases T ₅₀ , but so far, no clinical trials have investigated whether increasing serum magnesium increases serum calcification propensity in subjects with ESKD. Design, setting, participants, & measurements We conducted a single-center, randomized, double-blinded, parallel group, controlled clinical trial, in which we examined the effect of increasing dialysate magnesium from 1.0 to 2.0 mEq/L for 28 days compared with maintaining dialysate magnesium at 1.0 mEq/L on T ₅₀ in subjects undergoing hemodialysis for ESKD. The primary end point was the value of T ₅₀ at the end of the intervention. Results Fifty-nine subjects were enrolled in the trial, and of these, 57 completed the intervention and were analyzed for the primary outcome. In the standard dialysate magnesium group, T ₅₀ was 233±81 minutes (mean±SD) at baseline (mean of days-7 and 0) and 229±93 minutes at follow-up (mean of days 21 and 28), whereas in the high dialysate magnesium group, T ₅₀ was 247±69 minutes at baseline and 302±66 minutes at follow-up. The difference in T ₅₀ between the two groups at follow-up (primary analysis) was 73 minutes (between-group difference; 95% confidence interval, 30 to 116; P<0.001), and the between-group difference in serum magnesium was 0.88 mg/dl (95% confidence interval, 0.66 to 1.10; P=0.001). Conclusions Increasing dialysate magnesium increases T ₅₀ and hence, decreases calcification propensity in subjects undergoing maintenance hemodialysis.