Background. The purpose of this randomized, double-blind, placebo-controlled pilot study was to determine the effectiveness of an intravenous glucose-insulin-potassium (GIK) infusion in preventing myocardial damage and maintaining cardiac performance in patients undergoing "off-pump" myocardial revascularization. Methods. Forty-six adult patients undergoing elective off-pump coronary artery bypass received either normal saline or a GIK infusion immediately after the induction of anesthesia through the first 12 hours of intensive care unit convalescence. Measurements of blood glucose, circulating creatine kinase MB and troponin I concentrations, as well as cardiac index (CI) and mixed venous oxygen saturation (SvO2), were obtained immediately before starting the infusion (baseline) and at 6,12, and 24 hours post-initial coronary artery occlusion. Results. Five patients (8%) requiring cardiopulmonary bypass were excluded from data analysis. Twenty patients received saline. Twenty-one received GIK. Blood glucose was significantly higher in the GIK group. The concentration of circulating creatine kinase MB and troponin I significantly increased over time after off-pump coronary artery bypass, with no significant intergroup differences. Cardiac index and SvO2 did not differ significantly between groups. Conclusions. A GIK infusion protocol commonly used as an adjunct to reperfusion therapy for acute myocardial infarction causes insulin-resistant hyperglycemia in elective off-pump coronary artery bypass patients with no demonstrable benefit. The finding of significant release of cardio-specific enzymes in individual patients implies an ongoing need to develop more effective strategies for myocardial protection during off-pump coronary artery bypass.