Surgically induced ischemia and reperfusion injury continue to be a major contributor to morbidity and mortality after open heart surgery. Data about myocardial protection in high risk patients undergoing coronary artery bypass grafting (CABG) is scarce. Objective To evaluate the best technique of cardioplegic myocardial protection in high risk patients undergoing isolated or combined CABG and to assess the effect of giving warm (hot) shot cardioplegia before cross clamp removal on the immediate outcome of those patients. Methods Seventy-two patients who underwent either isolated or combined CABG at a tertiary care center in Saudi Arabia between January 2007 and July 2010 were enrolled. Data was prospectively and retrospectively collected and analyzed. The study populations are high risk patients (determined as simple additive EuroSCORE of 6 or more) for coronary artery bypass grafting. Patients are randomized into two groups comparing cold blood cardioplegia followed by warm shot as study group, and the control group using cold blood cardioplegia with no warm shot. The data collected included preoperative demographic and clinical characteristics, intraoperative data and postoperative short term outcome including inhospital mortality. Results A total of 72 patients were enrolled in 2 groups, hot shot group (group I, 32 patients) and non hot-shot patients group (group II, 40 patients). Patients receiving hot shots versus those not receiving hot shots were found to have significantly better outcome including fewer ventricular arrhythmias needing electric shock defibrillation (6.25% versus 17.55%, P= 0.005), intra-operative need of IABP (0% versus 5%, P