Coronary air embolism is a potential complication of cardiopulmonary bypass. We compared left ventricular function before and alter the administration of antegrade or retrograde cardioplegic solution in a porcine model of coronary air embolism. Nineteen pigs were placed on cardiopulmonary bypass support and cooled to 32°C. The heart was initially arrested with antegrade cold blood cardioplegic solution. The aortic crossclamp was released at 30 minutes and 0.02 cc/kg body weight of air was injected into the left anterior descending artery distal to the first diagonal branch. After 5 minutes the aorta was reclamped and the animals treated with 15 ml/kg body weight of 1:4 blood cardioplegic solution delivered by the antegrade (n = 6) or retrograde (n = 7) method. Control animals (n = 6) were not treated. Changes in regional preload recruitable stroke work were used to assess left ventricular performance before and after cardiopulmonary bypass. Two control animals could not be weaned from cardiopulmonary bypass. Left ventricular function was best preserved after treatment of induced coronary air embolism with retrograde cardioplegia (90% of baseline). Coronary air embolism treatment with antegrade cardioplegia resulted in diminished left ventricular performance (68% of baseline). In control animals left ventricular contractility was significantly impaired (39% of baseline). We conclude that administration of retrograde cardioplegic solution may be an effective method of treating coronary air embolism. The favorable outcome seen with cardioplegia may be in part because of its ability to protect the ischemic myocardium while the solution mechanically dislodges air from the vascular bed.