Background. This study was designed to evaluate the adenosine- triphosphate-sensitive potassium channel opener pinacidil as a blood cardioplegic agent. Methods. Using a blood-perfused, parabiotic, Langendorff rabbit model hearts underwent 30 minutes of normothermic ischemia protected with blood cardioplegia (St. Thomas' solution [n = 8] or Krebs-Henseleit solution with pinacidil [50 μmol/L, n = 8]) and 30 minutes of reperfusion. Percent recovery of developed pressure, mechanical arrest, electrical arrest, reperfusion ventricular fibrillation, percent tissue water, and myocardial oxygen consumption were compared. Results. The percent recovery of developed pressure was not different between the groups (52.3 ± 5.9 and 52.8 ± 6.9 for hyperkalemic and pinacidil cardioplegia, respectively). Pinacidil cardioplegia was associated with prolonged electrical and mechanical activity (14.4 ± 8.7 and 6.1 ± 3.9 minutes), compared with hyperkalemic cardioplegia (1.1 ± 0.6 and 1.1 ± 0.6 minutes, respectively; p < 0.05). Pinacidil cardioplegia was associated with a higher reperfusion myocardial oxygen consumption (0.6 ± 0.1 versus 0.2 ± 0.0 mL/100 g myocardium/beat; p < 0.05) and a higher percent of tissue water (79.6% ± 0.7% versus 78.6% ± 1.2%; p < 0.05). Conclusions. Systolic recovery was not different between groups, demonstrating comparable effectiveness of pinacidil and hyperkalemic warm blood cardioplegia.