Background: To evaluate the myocardial protective effect of nicorandil when used as an adjuvant to cold hyperkalaemic cardioplegia in open-heart surgery. Methods: Patients who underwent surgery under cardiopulmonary bypass (CPB) for mitral valve replacement (MVR, 23 patients) or coronary artery bypass grafting (CABG, 24 patients) were entered in a double-blind study. The patients were randomized to a nicorandil Group (N) or placebo Group (P). Nicorandil 0.1 mg kg−1 (Group N), or normal saline (Group P), were administered at three time points: (1) after aortic cannulation, but prior to going on CPB, (2) 5 min before aortic cross-clamping and (3) 5 min before reperfusion. The following variables were studied: (a) time until electromechanical arrest after cardioplegia administration (Tarrest), (b) time until return of electromechanical activity after aortic cross-clamp removal (Trecovery), (c) incidence of postoperative myocardial infarction or low output syndromes (d) dysrhythmias requiring intervention after aortic cross-clamp removal and (e) haemodynamic changes after nicorandil administration. Results: The Tarrest after cardioplegia administration was significantly faster in nicorandil group in both MVR and CABG patients (P < 0.05), but Trecovery did not differ significantly. The incidence of postoperative serum CK-MB > 75 IU L−1 in MVR patients was significantly lower in the Group N than in placebo patients (P < 0.05). However, in CABG patients there was no such significant difference. The incidence of dysrhythmias requiring intervention after aortic cross-clamp removal was also less in Group N. Administration of 0.1 mg kg−1 boluses of nicorandil did not cause significant haemodynamic changes or precipitate dysrhythmias in any patient. Conclusion: Nicorandil enhances the myocardial protective effect of cold hyperkalaemic cardioplegia in cardiac surgery patients.