Background and study aims We aimed to assess the efficacy and safety of the starting position during colonoscopy. Patients and methods We searched CENTRAL, MEDLINE, EMBASE, and the WHO International Clinical Trials Registry Platform through February 2019 to identify studies reporting the comparison between the right/supine/prone/tilt-down and left lateral starting position during colonoscopy. The primary outcomes were mean cecal insertion time and adverse events requiring medication. Two reviewers performed study selection and risk of bias assessment. We determined the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation method. This study was registered in PROSPERO (CRD42019124360). Results We identified 10 randomized controlled trials (RCTs) (2083 participants), including three trials on right/tilt-down versus left, two trials on supine/prone versus left, respectively. Mean difference in mean cecal insertion time in supine versus left was -41.0 s (95 % confidence interval [CI] -57.3 to -24.7) in one study and in tilt-down versus left was - 37.3 s (95 % CI -72.1 to -2.4; I 2 = 58 %) in three studies; however, there were no statistically significant differences in prone/right versus left position (very low certainty of evidence). Four of eight studies noted adverse effects requiring medication (moderate certainty of evidence). One RCT applying the tilt-down position was terminated because of increased occurrence of oxygen desaturation. Conclusion We could not conclusively determine the efficacy and safety of the starting position during colonoscopy because of low certainty of evidence. Further studies are needed to confirm the efficacy and safety of the starting potion during colonoscopy.