© 2015 National Kidney Foundation, Inc. Background: In the general population, low serum magnesium levels are associated with poor outcomes and death. While limited data suggest that low baseline magnesium levels may be associated with higher mortality in hemodialysis (HD) patients, the impact of changes in magnesium levels over time is unknown. Study Design: We examined the association of time-varying serum magnesium levels with all-cause mortality using multivariable time-varying survival models adjusted for clinical characteristics and other time-varying laboratory measures. Setting & Participants: 9,359 maintenance HD patients treated in a large dialysis organization between 2007 and 2011. Predictor: Time-varying serum magnesium levels across 5 magnesium increments (<1.8, 1.8-<2.0, 2.0-<2.2, 2.2-<2.4, and ≥2.4. mg/dL). Outcome: All-cause mortality. Results: 2,636 individuals died over 5 years. Time-varying serum magnesium levels < 2.0. mg/dL were associated with higher mortality after adjustment for demographics and comorbid conditions, including hypertension, diabetes, and malignancies (reference: magnesium, 2.2-<2.4. mg/dL): adjusted HRs for serum magnesium level < 1.8 and 1.8 to <2.0. mg/dL were 1.39 (95% CI, 1.23-1.58; . P . <. 0.001) and 1.20 (95% CI, 1.06-1.36; . P =0.004), respectively. Some associations were attenuated to the null after incremental adjustment for laboratory test results, particularly serum albumin. However, among patients with serum albumin measurements, low albumin level (<3.5. g/dL) and magnesium level < 2.0. mg/dL were associated with an additional death risk (adjusted HR, 1.17; 95% CI, 1.05-1.31; . P =0.004), whereas patients with high serum albumin levels (≥3.5. g/dL) exhibited low death risk (adjusted HRs of 0.53 and 0.53 [. P . ≤. 0.001] for magnesium < 2.0 and ≥2.0. mg/dL, respectively; reference: albumin < 3.5. g/dL and magnesium ≥ 2.0. mg/dL). Limitations: Causality cannot be determined, and residual confounding cannot be excluded given the observational study design. Conclusions: Lower serum magnesium levels are associated with higher mortality in HD patients, including those with hypoalbuminemia. Interventional studies are warranted to examine whether correction of hypomagnesemia ameliorates adverse outcomes in this population.