Does nicorandil instead of supranormal potassium safely provide cardioplegia and cardioprotection in humans? Fifty patients eligible for coronary artery surgery were randomly divided into two groups; one group received standard St Thomas' Hospital solution (STHS) and the other group got a crystalloid solution in which supranormal potassium was replaced with 0.2 mmol/l nicorandil. We measured time to arrest, rhythm abnormalities, pre- and postoperative troponin-T, CK-MB and myoglobin release as well as hemodynamic parameters. Time to arrest was significantly shorter in the STHS group (41.0+/-16.8 s) than in the nicorandil group (120.9+/-78.8 s, P<0.001). Four patients in the nicorandil group needed additional STHS to achieve satisfactory cardiac arrest. Troponin-T was elevated in the nicorandil group at four (P=0.042) and at eight (P=0.044) hours after surgery, myoglobin levels were elevated at 0 h after surgery (P=0.014), CK-MB levels were not group different. Hemodynamic performance was similar in both groups. Potassium should probably not be replaced by nicorandil alone in the cardioplegic solution. This study of low-risk patients with short (43.2 min) aortic cross-clamp times showed similar cardioprotection as revealed by hemodynamic performance whereas early release of troponin-T and myoglobin release in the nicorandil group raised some concern.