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Ursodeoxycholic acid (UDCA) may modify the risk of inflammatory bowel disease (IBD)–associated colorectal cancer. We performed a systematic review and meta-analysis of studies evaluating the effect of UDCA on the risk of IBD-associated colorectal neoplasia (CRN) (defined as colorectal cancer and/or dysplasia) in patients with primary sclerosing cholangitis with concomitant IBD (PSC-IBD).We conducted a systematic search of Medline, Embase, and Web of Science and manually reviewed the literature. Studies were included if they: (1) evaluated exposure to UDCA in patients with PSC-IBD, (2) reported IBD-associated CRN as outcome, and (3) reported relative risks or odds ratios (ORs) or provided data for their calculation. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random-effects model.Eight studies (5 observational, 3 randomized controlled trials) reporting 177 cases of CRN in 763 patients with PSC-IBD were included in the analysis. Overall, meta-analysis showed no significant protective association between UDCA use and CRN (OR, 0.81; 95% CI, 0.41–1.61). However, there was a significant chemopreventive effect on the risk of advanced CRN (colorectal cancer and/or high-grade dysplasia) (OR, 0.35; 95% CI, 0.17–0.73). In a subgroup analysis, low-dose UDCA use (8–15 mg/kg/d) was associated with significant risk reduction of CRN (OR, 0.19; 95% CI, 0.08–0.49).UDCA, particularly at low doses, may reduce the risk of advanced CRN in patients with PSC-IBD. However, results should be interpreted with caution, given limited reporting of cancer-related outcomes, primarily from tertiary care centers.