Twenty-six healthy mixed-breed dogs (25 to 35 kg) underwent hypothermic (27 C) cardiopulmonary bypass. The heart was arrested with cold (4 C) cardioplegic solution, and left ventriculostomy performed. Postoperative mortality was 11.5% (3/26). Two deaths were attributable to ventricular fibrillation the night after surgery, and one death 2 weeks later was the result of pulmonary embolization. All other dogs recovered promptly and were well at follow-up evaluation 6 weeks later. The most important considerations were (1) the surgical approach, ie, combining left lateral thoracotomy with cannulation of the right atrium and left femoral artery for cardiopulmonary bypass (CPB) (avoiding median sternotomy and aortic arch perfusion), (2) the adherence to strict criteria for CPB perfusion, consisting of blood flow of at least 2.2 L/m2/min, PCV no less than 25%, gas flow through the oxygenator (97% O2, 3% CO2) of at least 3.5 L/min, maintenance of a mean arterial blood pressure greater than 60 mm of Hg, and heparinization to maintain activated clotting time over 480 seconds, (3) the use of dipyridamole infusion to preserve platelets during CPB, resulting in decreased postoperative blood loss and (4) the monitoring of cardiac, respiratory, renal, and neurologic functions before, during, and after the operation, with particular emphasis on fluid balance and electrolytes. We concluded that a high success rate is possible for open-heart surgery in the dog requiring cardiopulmonary bypass, but only through meticulous surgical technique and the combined application of many monitoring techniques, with timely intervention to correct serious departures from homeostasis.