Background: Previous small to mid-sized studies have found an inconsistent relationship between diverticulosis and colon polyps. We assessed the odds of polyps in patients with left-sided diverticulosis (LDV) compared with patients without LDV, and if a predilection for polyps existed in the distal colon (DC) versus the proximal colon (PC). Methods: In this case-control, retrospective study, records of all patients in the Cleveland Clinic undergoing average-risk, screening colonoscopy between January 2011-August 2017 were identified. Baseline characteristics were described. Multivariate logistic regression analysis was performed to identify odds of polyps in PC and DC after adjusting for clinical and colonoscopic factors. Results: A total of 50,703 patients (mean age=60 years; 48% male) were included; 38.9% of patients had LDV. Compared to patients without LDV, those with LDV more often had adenomas (33.2% vs 27.8%; P<0.001), hyperplastic polyps (HPs) (18.3% vs 16.2%; P<0.001), and sessile serrated polyps (SSPs) (4.8% vs 4.3%; P=0.