Nitric oxide (NO) supplementation may modify myocardial oxygen consumption and vascular function after ischemia. We investigated the effects of the NO donor, S-nitroso human serum albumin (S-NO-HSA), on cardiac oxygen metabolism during controlled reperfusion on normothermic cardiopulmonary bypass after severe myocardial ischemia. Pigs randomly received either S-NO-HSA or human serum albumin prior to and throughout global myocardial ischemia. Myocardial oxygen utilization is impaired at the onset of reperfusion, which is not amenable to S-NO-HSA. However, NO supplementation during ongoing supply dependency of oxygen consumption eventually leads to greater myocardial oxygen delivery and consumption. In conjunction with a better washout of lactate, this indicates an improved capillary perfusion in the S-NO-HSA group during reperfusion, which results in a better contractile function post bypass.