This report summarizes the five years of laboratory investigations and the initial six-month clinical experience with a calcium antagonist, nifedipine, added to a cold hyperkalemic cardioplegic solution for enhancement of myocardial protection. Regional ischemia was created in 112 dogs and global ischemia in 98 dogs, under normothermic and two hypothermic states. Control solutions, two clinical cardioplegic solutions, and nifedipine solutions were compared. Infusion of nifedipine during regional ischemia and reperfusion intervals resulted in a two-to-threefold reduction in injury volume and maintenance of normal left ventricular function in contrast to infusion of nitroprusside. Nifedipine solutions (0.2 μg/ml) provided superior preservation of left ventricular function in comparison to the two cardioplegic solutions after one hour of global ischemia at 37°C and two hours at 18°C. In a clinical trial of nifedipine in cold potassium cardioplegia, 38 high risk patients with poor ventricular function have been treated; 22 of which were intensively studied serially with radionuclide ventriculography and pyrophosphate scans, myocardial isoenzyme determinations, 24 hour EKG recordings and intra- and and postoperative hemodynamic studies. Of the 35 patients admitted to the intensive care unit (ICU), 33 have survived. Stroke work and cardiac indices return promptly to near normal levels after operation. The time-isoenzyme activity curves are low and radionuclide determined ejection fractions show no change for the study group. Death from acute postischemic cardiac failure did not occur in treated patients and the usage of intra-aortic balloon pump (IABP) has decreased threefold in comparison with 40 similar high risk patients treated concurrently with cardioplegic solution alone. It is concluded that nifedipine is a potent adjunct to cold hyperkalemic cardioplegic solution in high risk patients.