Background: Recent observations have associated hypomagnesemia with increased risk of cardiovascular morbidity and mortality in hemodialysis patients. Methods: We did a 3-month chart review of 62 chronic hemodialysis patients at a single US hospital. All were dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/l. Patients were divided into two groups: hypomagnesemic (mean predialysis plasma [Mg] <1.5 mEq/l) and non-hypomagnesemic (mean predialysis plasma [Mg] ≥1.5 mEq/l). Results: All patients were male; mean age was 64.3 ± 8.7 years and the majority (73%) diabetic. 24 patients (39%) had hypomagnesemia and 38 (61%) were not hypomagnesemic. There were no significant differences between the two groups in age, diabetes status, blood pressure, duration of dialysis, plasma calcium, phosphorus, albumin, intact parathyroid hormone (PTH), dialysis adequacy (Kt/V), or dietary protein intake (as estimated by normalized protein catabolic rate, nPCR). However, use of proton pump inhibitors (PPIs) was significantly associated with hypomagnesemia (plasma [Mg] 1.48 ± 0.16 mEq/l in the PPI group vs. 1.65 ± 0.26 mEq/l in the non-PPI group, p = 0.007). Adjustment for age, diabetes status, duration of dialysis, plasma albumin, Kt/V, nPCR, and diuretic use did not affect the association between PPI use and hypomagnesemia. Conclusions: Use of PPIs in patients dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/l is associated with hypomagnesemia. We suggest monitoring plasma [Mg] in patients taking PPIs, with discontinuation of the medication if possible and/or adjustment of dialysate [Mg] to normalize plasma [Mg].