Objective: Magnesium (Mg2+) is cardioprotective and has been routinely used to supplement cardioplegic solutions during coronary artery bypass graft (CABG) surgery. However, there is no consensus about the Mg2+ concentration that should be used. The aim of this study was to compare the effects of intermittent antegrade warm-blood cardioplegia supplemented with either low- or high-concentration Mg2+. Methods: This study was a randomised controlled trial carried out in two cardiac surgery centres, Bristol, UK and Cuneo, Italy. Patients undergoing isolated CABG with cardiopulmonary bypass were eligible. Patients were randomised to receive warm-blood cardioplegia supplemented with 5 or 16 mmol l−1 Mg2+. The primary outcome was postoperative atrial fibrillation. Secondary outcomes were serum biochemical markers (troponin I, Mg2+, potassium, lactate and creatinine) and time-to-plegia arrest. Intra-operative and postoperative clinical outcomes were also recorded. Results: Data from two centres for 691 patients (342 low and 349 high Mg2+) were analysed. Baseline characteristics were similar for both groups. There was no significant difference in the frequency of postoperative atrial fibrillation in the high (32.8%) and low (32.0%) groups (risk ratio 1.03, 95% confidence interval, CI, 0.82–1.28). However, compared with the low group, troponin I release was 28% less (95% CI 55–94%, p = 0.02) in the high-Mg2+ group. The 30-day mortality was 0.72% (n = 5); all deaths occurred in the high-Mg2+ group but there was no significant difference between the groups (p = 0.06). Frequencies of other major complications were similar in the two groups. Conclusions: Warm-blood cardioplegia supplemented with 16 mmol l−1 Mg2+, compared with 5 mmol l−1 Mg2+, does not reduce the frequency of postoperative atrial fibrillation in patients undergoing CABG but may reduce cardiac injury. (This trial was registered as ISRCTN95530505.)