Background: The objective of this study was to compare the efficacy and safety of propofol and general anesthesia in children undergoing elective GI endoscopy. Methods: The study design was prospective, randomized, and open label. Pediatric patients aged 2 to 21 years in whom elective GI endoscopy under general anesthesia was required were randomized to receive propofol or standard inhalational anesthesia. The parameters monitored in the 2 groups were (1) time until wake-up after completion of the procedure, and (2) total time for anesthesia and recovery. Adverse events during the procedures were noted with each agent. Results: Fifty pediatric patients were recruited, 25 in each group. The mean (SD) time until wake-up in the propofol group was 29.92 (16.01) minutes and 18.52 (10.03) minutes in the anesthesia group, (p = 0.002). With stratification into 4 age groups, it was noted that the youngest children, those 2 to 5 years of age, took the longest to awaken with propofol compared with inhalational anesthesia, whereas in the other age groups the differences were not statistically significant. In contrast, the mean total time for anesthesia and recovery in the propofol group was 107.4 (30.14) minutes and 139 (7.61) minutes in the inhalational anesthesia group (p < 0.004). The total time for anesthesia and recovery was longest in the group 5 to 8 years of age who had inhalational anesthesia (p < 0.01). Changes in systolic and diastolic blood pressure occurred with equal frequency in both groups. Transient apnea was noted in 20% of patients receiving propofol. Restlessness and agitation occurred in 52% of patients receiving inhalational anesthesia compared with 8% in the propofol group (p = 0.001). Conclusions: Propofol, administered by an anesthesiologist, is an excellent and safe intravenous anesthetic agent for pediatric GI endoscopy.