Objective To investigate the gastrointestinal(GI) protective effect of Omeprazole on children undergoing thoracoscopic heart surgery with cardiopulmonary bypass (CPB). Methods One hundred and twenty seven patients who were scheduled for cardiac surgery with CPB were randomly equally divided into three groups. Group A and B underwent thoracoscopic heart surgery, while the control group underwent conventional heart surgery by sternotomy. Before CPB, group A was treated with Omeprazole 10mg added to the priming solution.? Group B and the control group were treated by adding the same amount of normal saline (to the priming solution). pH and red blood cell count of gastric secretion and serum gastric level (Assay Designs ELISA) were measured at the following intervals: before CPB, 30 minutes into CPB, at termination of CPB,4 and 24 hours after termination of CPB. Results Compare to prior to CBP, the value of the gastric pH in group A was significantly higher (Plt;0.01), and that of group B was significantly lower (Plt;0.05)at the end of CPB. The same value in the control group was significantly lower (Plt;0.05)4h, after the end of CPB. Compared to prior CPB, the mean red blood cell count of gastric secretion and serum gastric level were significantly descent (Plt;0.01) in all there group post CBP. Compare to the control group, the mean gastric pH level in group A was significantly elevated at all time intervals post CBP; while the mean gastric secretin red blood cell count was significantly decreased. The mean serum level in group A 30 min post CBP was significantly lower than that in group B and the control group. Compared to the control group, the mean gastric pH level was significantly lower in group B but returned to the pre-CPB level in 24 h. The mean gastric secretin red blood cell amount and serums gastric level in group B at all time intervals were significantly decreased compare to those of the control group. Conclusion Thoracoscopic heart surgery of children with CPB