Objective: To observe insulin resistance (IR) during infant cardiopulmonary bypass (CPB), and determine the effect of IR on prognosis of infants with congenital heart disease. Methods: We collected 60 infants with congenital ventricular septal defect who were performed CPB surgery from March 2012 to March 2013, and selected 5 time points, including 5 min after anesthesia induction, before CPB starting, 15 min after the CPB starting, 5 min after aortic clamping, and 15 min at the end of CPB. Blood glucose and plasma insulin were checked to calculate insulin resistance index (HOMA-IR). We also simultaneously recorded the infants’s aortic clamping time, CPB time, and postoperative duration of mechanical ventilation. The peak value of HOMA-IR was used as a cut-off point between high and low IR group and the difference in duration of mechanical ventilation between 2 groups was compared. Results: The insulin, glucose, and HOMA-IR value in the perioperative period increased gradually at 5 min after anesthesia induction, and achieved the peak value at 5 min after aortic clamping. There were significant difference between other time points and the point of 5 min after anesthesia induction(P<0.05 or P<0.01). The duration of mechanical ventilation in the high IR group was much longer than that in the low IR group (P<0.05). Conclusion: The degree of metabolic disorder stress caused by CPB surgery can affect the prognosis of infants with congenital heart disease and reducing IR level and easing the endocrine and metabolic disorder are important for improving the prognosis.