Objective To explore the reasonable withdrawal time at different colonic segments. Methods It was a prospective observational study involving 465 patients who underwent colonoscopy from November 2019 to November 2020 at our endoscopy center. Colonoscopy records in our center from July 2017 to September 2017 were retrospectively analyzed as a validation set. Results The cut-off values of withdrawal time at ascending colon, transverse colon, descending colon, and sigmoid colon and rectum determined by receiver operating characteristic (ROC) curve were 77 s, 61 s, 56 s, and 109 s, respectively. At the ascending colon, the adenoma detection rate (ADR) was significantly higher (17.3% VS 2.8%, P＜0.001) when the colonoscopy withdrawal time was ≥77 s. When the withdrawal time was ≥61 s at the transverse colon (6.9% VS 2.8%，P=0.036), that over 59 s at the descending colon (6.3% VS 1.7%，P=0.019), and that ≥109 s at the sigmoid colon and rectum (31.0% VS 7.9%，P＜0.001), the ADR was significantly higher. Multivariate analysis showed that withdrawal time of ≥77 s at the ascending colon (OR=6.427, P＜0.001), those ≥56 s at the descending colon (OR=3.564, P=0.045) and ≥109 s at the sigmoid colon and rectum (OR=5.073, P＜0.001) were independent risk factors for the increase of ADR. In the validation set, when the withdrawal times at the ascending colon, the transverse colon, the descending colon, and the sigmoid colon and rectum were ≥77 s, 61 s, 56 s, and 109 s, respectively, the total ADR (48.3% VS 17.6%, OR=2.952, P<0.001) and polyp detection rate (PDR) (63.2% VS 23.0%, OR=4.191, P<0.001) significantly increased. There were no significant differences in ADR (P=0.563) or PDR (P=0.770) compared with those where withdrawal time was over 6 min. Conclusion The ADR and PDR significantly increase when the withdrawal times are ≥77 s at the ascending colon, ≥61 s at the transverse colon, ≥56 s at the descending colon, and ≥109 s at the sigmoid colon and rectum.