Background: Cardiac and pulmonary veins de-airing are of the most important steps during open heart surgery. This study evaluates the effect of continuous positive airway pressure (CPAP) on air trapping in pulmonary veins and on quality of de-airing procedure. Materials and Methods: This randomized prospective double blind clinical trial conducted on 40 patients. In the control group: During cardiopulmonary bypass (CPB), the ventilator was turned off and adjustable pressure limit (APL) valve was placed in SPONT position. In CPAP group: During CPB, after turning the ventilator off, the flow of oxygen flow was maintained at the rate of 0.5 L/min and the APL valve was placed in MAN position on 20 mbar. During cardiopulmonary bypass (CPB) weaning, the patients were observed for air bubbles in left atrium by using transesophageal echocardiography. Results: The mean de-airing time after the start of mechanical ventilation in CPAP group (n = 20) was significantly lower than the control group (n = 20) (P = 0.0001). The mean time of the left atrium air bubbles occupation as mild (P = 0.004), moderate (P = 0.0001) and severe (P = 0.015) grading was significantly lower in CPAP group. Conclusions: By CPAP at 20 mbar during CPB in open heart surgery, de-airing process can be down in better quality and in significantly shorter time.