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Background: One-day low-residue diet (LRD) is recommended before colonoscopy, but only three single-center trials compared the 1-day versus 3-day LRD. The aim of this multicenter study was to compare the impact of a 3-day versus 1-day LRD on its ability to adequately and successfully prepare the bowel of outpatients that require a colonoscopy. The outpatients' tolerance and adherence to the LRD were also considered. Methods: Consecutive outpatients were randomized to 1-day versus 3-day LRD at three open-access endoscopy units. The primary endpoint consisted of the proportion of patients with a satisfactory degree of bowel cleanliness (Score 2–3 on the Boston Bowel Preparation Scale [BBPS] in each segment). Secondary endpoints were patients' tolerance and adherence to the prescribed diet evaluated by a standardized questionnaire. Results: 289 patients were included in the study (1-day LRD arm = 143, 3-day LRD arm = 146). BBPS ≥2 was not significantly different in the two dietary regimens in any of the three colonic segments (71% vs. 72%, p = 0.9). The percentage of patients with incomplete preparation was similar in the two arms (9% vs. 9%; p = 1.0). No significant differences were found among colonoscopy findings in terms of abnormalities (81% vs. 84%, p = 0.8). Both groups scored similarly in overall tolerance to LRD (48% vs. 49%, p = 1.0) and also in whether they would have adopted a different dietary regimen (p = 0.3). Conclusion: Our multicenter randomized study confirmed that optimal bowel cleansing is reached through a 1-day LRD. [ABSTRACT FROM AUTHOR]