To assess the efficacy of pulsatile flow in minimizing reperfusion injury following cardioplegic arrest, 20 dogs supported by cardiopulmonary bypass underwent 60 minutes of hypothermic, hyperkalemic crystalloid cardioplegic arrest. The effects of pulsatile flow (Group 2), initiated during 30 minutes of reperfusion, on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores, coronary blood flow, and myocardial water content were compared with the effects of linear flow reperfusion (Group 1). Myocardial ATP stores were maintained at preischemic levels by this mode of myocardial protection. However, pulsatile flow prevented the significant decline in ATP levels incurred during linear reperfusion. Creatine phosphate stores, although depleted during arrest, were restored equally, regardless of the mode of reperfusion. The decline in ATP stores was associated with no pathological increase in myocardial water content, but was associated with persistent reactive hyperemia. In contrast, after 30 minutes of pulsatile reperfusion, coronary blood flow was significantly decreased compared with preischemic flow. These data indicate that pulsatile reperfusion can prevent the unique decline in ATP levels associated with the restoration of coronary flow after cardioplegic arrest (reperfusion injury), and support its continuing evaluation as an adjunct to adequate intraoperative myocardial protection.