AbstractAimTo evaluate whether the use of a laxative with reduced patient burden in oral antibiotics and mechanical bowel preparation (OAMBP) could prevent surgical site infection (SSI) in left‐sided colon and rectal cancers.MethodsThis multicenter, non‐blinded, randomized, non‐inferiority trial included patients who underwent elective colorectal surgery for colorectal cancer in a university and community hospital in Japan from April 1, 2021 to March 31, 2023. We compared conventional OAMBP (polyethylene glycol, metronidazole, and kanamycin) (cOAMBP group) with modified OAMBP (sodium picosulfate hydrate, metronidazole, and kanamycin) (mOAMBP group). The primary outcome was overall incidence of SSI. Secondary outcomes were postoperative complications, degree of patient burden, and intraoperative bowel dilatation.ResultsAmong 119 patients, 112 were randomly assigned to the two groups, with 56 patients in each group. SSI occurred in three (5.4%) and five patients (8.3%) in the mOAMBP and cOAMBP groups, respectively (90% confidence interval [CI]: −12.8–5.3), with a 15% margin of non‐inferiority. Anastomotic leakage occurred in no patient in the mOAMBP group and three patients (5.4%) in the cOAMBP group (p = 0.24). The cOAMBP group reported significantly more pain than the mOAMBP group (50 [90.9%] vs. 7 [12.5%] participants). The mOAMBP group showed significantly lesser bowel dilatation than the cOAMBP group (1 [1.8%] vs. 21 [37.5%] participants).ConclusionmOAMBP is safe and less burdensome, can reduce intraoperative bowel dilatation, and is non‐inferior compared with cOAMBP in preventing SSI. Therefore, mOAMBP may be more suitable for sigmoid colon and rectal cancer.Trial RegistrationUMIN000043162 (http://www.umin.ac.jp/ctr/). Registered on January 28, 2021.