Background and Aim Endoscopic examinations carry a potential risk of cross‐infection, and the traditional reprocessing method is time consuming. We evaluated the safety and efficacy of a novel disposable sheathed gastroscope system in clinical practice in comparison with the conventional gastroscope. Methods There were two phases in the study. In phase 1, 20 patients with hepatitis B were randomized into two groups: the sheathed group was examined with the novel disposable sheathed gastroscope (n = 10) and the conventional group with the conventional gastroscope (n = 10). Microbiologic tests were performed on each endoscope afterwards. In the second phase, 1120 patients were randomized again into the same two groups with 568 and 552 patients in the sheathed group and the conventional group, respectively. The time duration of the endoscopic procedure and reprocessing were measured. The pathology detection rate of endoscopic examinations, the patients' subjective feelings, and problems occurred during procedures were also recorded. Results The total instrument turn‐around time in the phase 2 sheathed group (9.9 ± 1.3 min) was significantly shorter than the conventional group (39.0 ± 1.4 min, P = 0.000). The mean procedural time was slightly longer in the sheathed group than in the conventional group (4.9 ± 1.4 vs 4.1 ± 1.3 min, P = 0.000). However, the duration of endoscopic reprocessing was much shorter (4.9 ± 0.2 vs 35 ± 0.2 min, P = 0.000). No significant differences were observed in patient discomfort, optical clarity, or pathology detection rate. There were no complications in either group, and no microbial contamination was detected in phase 1 of the study. Conclusions Compared with the conventional gastroscope, the novel disposable sheathed gastroendoscope is safe and more efficient in clinical practice.