Back ground: Arterial switch operation for correction of transposition of great arteries requires long duration of cardiopulmonary bypass (CPB) support. The subsets of patients for arterial switch operation (ASO) are neonates and infants. Hypothermic CPB can lead to severe vasoconstriction in small vessels and hamper the tissue perfusion in small children. Phenoxybenzamine because of its potent vasodilatory effect will help in improving microcirculatory perfusion to the vital organs during CPB and reduce reperfusion injury. Method: In a prospective study, 45 infants undergoing ASO were divided into 3 groups 15 patients in each group. Group 1 and 2 received phenoxybenzamine 1mg/kg and 0.5mg/kg respectively during CPB and Group 3 was the control group who did not receive phenoxybenzamine. The effect of phenoxybenzamine was assessed by monitoring aortic line pressure, mean arterial pressure, nasopharyngeal and rectal temperatures, venous oxygen saturation, cerebral oxygenation by near infrared spectroscopy and base deficit were measured at 10 minutes interval during CPB in 3 groups. Result: Patients of group 1 and 2 showed significant fall in aortic line pressure and mean arterial pressure (p<0.05-0.000) compared to group 3. Group 1 and 2 had higher venous oxygen saturation and cerebral oxygenation (p<0.04-0.001) compared to Group 3. The temperature gradient was lower in Group 1 and 2 (p=0.01-0.004). The base deficit was more in Group 3 patients (p=0.005). Group 1 children had lower aortic line pressure and mean arterial pressure than Group 2 (p=0.000), with higher venous oxygen saturation and cerebral oxygenation (p=0.000). Conclusions: Phenoxybenzamine during CPB produces lower aortic line and facilitates for higher pump flow; resulting in higher venous and cerebral oxygenation, faster cooling and re-warming, and less base deficit. Phenoxybenzamine in a dose of 1mg/kg was more effective than 0.5mg/kg.