The effects of retrograde and antegrade delivery of cold St. Thomas' Hospital cardioplegia were evaluated and compared in 21 patients who underwent elective myocardial revascularization. The patients were randomly separated into two groups: the antegrade group (n = 10), and the retrograde group (n = 11). Cardiac energy metabolism was monitored by evaluation of arterial and coronary sinus (CS) lactate concentration. There was an increase of the CS lactate concentration during aortic cross-clamp period in both groups. After release of the aortic cross-clamp, there was an increase of the CS lactate concentration in the antegrade group, and a decrease of CS lactate in the retrograde group. Analysis of the patients operated with antegrade delivery of cardioplegia showed an increase of the CS lactate concentration in 9/10 patients after aortic cross-clamp release. In the retrograde group, in 8/11 patients the CS lactate concentration decreased immediately after aortic cross-clamp release. Whereas the differences in the CS lactate concentration were not significantly different, the lactate extaction immediately after aortic cross-clamp release was significantly higher for the retrograde group (p = 0.034). This can be related to a faster reconsolidation of mitochondrial oxidative phosphorylation in the retrograde group. For the other registered parameters, hemodynamic recovery of cardiac function, release of creatine kinase MB isoenzyme, and clinical outcome, there was no significant difference between the groups. Based on this study we conclude that retrograde delivery of a cold non-oxygenated cardioplegic solution results in a better preservation of myocardial energy reserve than antegrade delivery.