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Background: Cardiopulmonary bypass (CPB) during cardiac surgery has some adverse effects on pulmonary physiology by different mechanisms. This study was designed to compare the effect of different modes of ventilation applied during cardiopulmonary bypass on peri-operative respiratory parameters of the patients. Methods: After approval of Research Committee and obtaining informed consent, this randomized, double-blinded clinical trial study was conducted. 150 patients undergoing coronary artery bypass graft surgery in Chamran Heart Hospital, in Isfahan, were randomly allocated into three groups (50 patients in each group). Group 1 received CPAP with PEEP=10cmH2O, FiO2=20%. Group 2 received CPAP with PEEP=10cmH2O, FiO2=100%. Group 3 received no ventilation during bypass surgery. PaO2, PaCo2 and pH were recorded at 9 steps in 3 groups. In addition, static compliance and dynamic compliance were measured at 3 points in the 3 groups. All the data were analyzed by SPSS 17 using appropriate tests including Repeated Measures of ANOVA. Finding: The PaO2 measures were significantly higher in group (2) than the other 2 groups (p<0.001). PaO2 was lower in group (1) in comparison to other groups (p<0.001). Static Compliance and Dynamic Compliance were remarkably higher in patients of group (1) (p<0.001).  There was no difference in the length of ventilation in ICU among the groups. Conclusion: This study shows that administration of PEEP with a mixture of air and oxygen during CPB in cardiac surgery has beneficial effects on peri-operative respiratory parameters in patients.