Objective To evaluate the influence on the results and safety of double-balloon enteroscopy (DBE) at different combination time. Methods Patients who received combined DBE procedures in Nanjing Drum Tower Hospital from April 2019 to August 2020 were divided into the one-day combination group and the non-one-day combination group. The complete enteroscopy rate, time of anterograde approach, time of retrograde approach, total time of combined approach, adverse events, hospital stay and cost were compared. Results Among 119 patients who received DBE, 23 patients were excluded due to small intestinal stenosis. The complete enteroscopy rate was 92.9% (39/42) in the one-day group and 74.1% (40/54) in the non-one-day group, showing significant difference (χ2=4.390, P=0.036). There were significant differences in the time of retrograde approach (35.59±23.29 min VS 55.10±19.04 min, t=-4.080, P<0.001), total time of combined approach (89.10±27.82 min VS 114.20±24.55 min, t=-4.254, P<0.001), hospital stay (9.24±3.76 d VS 11.76±4.41 d, t=-2.599, P=0.011) between the two groups. There were no significant differences in the time of anterograde approach, hospital cost or adverse events between the two groups. Conclusion Combined DBE on one day yields a higher complete enteroscopy rate, less examination time and less hospital stay, which is worth of clinical application.