Background and hypothesis Association between hypo- and/or hypermagnesaemia and cardiovascular (CV) outcomes or mortality showed conflicting results in chronic kidney disease (CKD) and was conducted on total magnesium (tMg) levels. Thus, the objectives of the present study were to (i) describe the serum ionized Mg (iMg) concentration in patients at various CKD stages, (ii) measure the correlation between iMg and tMg concentrations, (iii) identify their associated factors and (iv) determine whether serum tMg and/or iMg concentrations are associated with major adverse cardiovascular events (MACE) and mortality before kidney replacement therapy (KRT) in CKD patients. Methods CKD-REIN is a prospective cohort of CKD patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2. Baseline iMg and tMg serum concentrations were centrally measured. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios (HRs) for first MACE and for mortality. Results Of the 2,419 included patients, median age was 68, and the mean eGFR was 34.8 mL/min/1.73 m². Concentrations of serum iMg and tMg were strongly correlated (r=0.89, p<0.001) and are independently associated with eGFR. The adjusted HR [95%CI] for MACE associated with the baseline serum tMg level was 1.27 [0.95; 1.69] for patients in tertile 1, and 1.56 [1.18; 2.06] for patients in tertile 3, relative to patients in tertile 2. The HR [95%CI] of death according to serum tMg concentration was increased in tertile 3 (1.48 [1.11; 1.97]). The adjusted risk for MACE and mortality (all-cause or CV) associated with the baseline serum iMg level was not significantly different between tertiles. Conclusions Our analysis of a large cohort of patients with moderate-to-advanced CKD demonstrated that individuals with higher serum tMg concentrations, although still within the normal range, had a greater likelihood of MACE and mortality. However, serum iMg levels were not associated with these outcomes.