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 T50, the time taken to convert from primary to secondary calciprotein particle in the serum. Lower T50 represents higher calcification propensity and is associated with higher risk of cardiovascular events and death in patients with ESKD. Increasing magnesium in serum increases T50, but so far, no clinical trials have investigated whether increasing serum magnesium increases serum calcification propensity in subjects with ESKD. 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 T50 in subjects undergoing hemodialysis for ESKD. The primary end point was the value of T50 at the end of the intervention. 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, T50 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, T50 was 247±69 minutes at baseline and 302±66 minutes at follow-up. The difference in T50 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). Increasing dialysate magnesium increases T50 and hence, decreases calcification propensity in subjects undergoing maintenance hemodialysis. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_08_21_CJASNPodcast_18_9_B.mp3. Copyright © 2018 by the American Society of Nephrology.