Objective To evaluate the performance, efficacy and safety of a novel portable endoscopy system for upper gastrointestinal examination. Methods A multicentered, open‑label, randomized, non‑inferiority controlled study was conducted in 3 clinical research centers from June 2019 to June 2020, and a total of 90 outpatients admitted to Department of Gastroenterology were randomly assigned to the trial group (n=44) undergoing portable endoscopy and the control group (n=46) undergoing Olympus endoscopy. The examination success rate, image quality, performance, overall operation satisfaction rate, biopsy success rate and adverse events of the two groups were compared. Results The examination success rates of the trial group and the control group were 97.73% (43/44) and 100.00% (46/46) respectively with a difference of -2.27% (95%CI: -6.68%-2.13%), higher than the set non-inferiority margin of -10%. Rates of good and excellent image quality were 100% in both groups, and the difference of 0 was higher than the set non-inferiority margin of -10%. There was no significant difference in the rate of good and excellent performance of the operating system between the two groups [97.67% (42/43) VS 100.00% (46/46), P=0.483]. There was significant difference in the overall satisfactory rate of the operation between the two groups [86.05% (37/43) VS 100.00% (46/46), P=0.011]. A total of 9 cases underwent endoscopic biopsy, including 5 cases in the trial group and 4 cases in the control group. The biopsy channels in both groups were smooth and the biopsy were successfully completed. There was no significant difference in adverse event rate between the two groups [25.00% (11/44) VS 10.87%(5/46), χ2=3.07, P=0.080]. All adverse events disappeared in 48 hours, and no severe adverse events or device defect events occurred. Conclusion The novel portable endoscopic system is comparable to Olympus endoscopic system in terms of the operating performance, the image quality and safety. Therefore, this system is safe and effective for upper gastrointestinal examination.