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Purpose: Anastomotic leak (AL) is a serious complication following colorectal surgery. Atherosclerosis causes inadequate anastomotic perfusion and is suggested to be a risk factor for AL. The aim of this study was to investigate the association of mesenteric occlusive disease on preoperative computed tomography (CT) scan with AL after left-sided colon or rectal cancer surgery., Methods: This was a retrospective, multicenter cohort study including 1273 patients that underwent left-sided or rectal cancer resection between 2009 and 2018 from three hospitals in the Netherlands. AL patients were 1:1 matched with non-leak patients and preoperative contrast-enhanced CT-scans were retrospectively analyzed for mesenteric atherosclerotic lesions. The main outcome measure was the presence of mesenteric occlusive disease on the preoperative CT-scan., Results: Anastomotic leak developed in 6% of 1273 patients (N = 76). Low anterior resection and stage I-III disease were statistically significant associated with AL (p = 0.01, p = 0.04). No other statistically significant differences in patient characteristics between AL and non-leak patients were found. A clinically significant stenosis (≥ 70-100%) of the inferior mesenteric artery was statistically significant more frequent present in AL patients, compared to non-leak patients (p < 0.01). No statistically significant differences in the presence of mesenteric occlusive disease of the celiac artery and superior mesenteric artery between AL patients and non-leak patients were found., Conclusion: Mesenteric occlusive disease of the IMA on preoperative CT-scan is associated with AL after left-sided colon or rectal resection for cancer. Preoperative identification of high-risk patients with a preoperative CT-scan of the mesenteric vasculature might be useful to reduce the risk of AL., (© 2022. The Author(s).)