BACKGROUND: Patients with long-standing colitis carry an increased risk of colorectal cancer and are therefore enrolled in colonoscopic surveillance programs. It is presently not known if endoscopic surveillance of patients with colitis with a closed rectal stump after a subtotal colectomy is justified. Neither is it clear which of these patients might be at increased risk for rectal stump cancer. OBJECTIVE: The aim of this study is to identify the risk factors for rectal stump cancer. DESIGN: This investigation is a retrospective descriptive case-control study. SETTINGS: This study was conducted at tertiary referral centers in the Netherlands. PATIENTS: Colorectal cancer cases associated with inflammatory bowel disease diagnosed between 1990 and 2006 were selected in a nationwide pathology archive. Patients with rectal stump cancer were selected from this group. The pathology archive was also used to identify inflammatory bowel disease controls matched for referral center with a closed rectal stump after subtotal colectomy, but without neoplasia. Follow-up started at the date of subtotal colectomy with the formation of a rectal stump. Demographic and disease characteristics were collected at baseline. MAIN OUTCOME MEASUREMENTS: Hazard ratios with 95% confidence intervals were calculated for factors associated with the development of rectal stump cancer with the use of univariate Cox regression analysis. End points were rectal stump cancer, end of follow-up, or death. RESULTS: A total of 12 patients with rectal stump cancer and 18 matching controls without neoplasia were identified. Univariate analysis showed an association between rectal stump cancer and primary sclerosing cholangitis, and disease duration until subtotal colectomy. LIMITATIONS: This study is limited by its retrospective design, and, despite being the largest series to date, it still has a limited number of cases. CONCLUSIONS: Risk factors for rectal stump cancer in a closed rectal stump after subtotal colectomy were primary sclerosing cholangitis and disease duration until subtotal colectomy. © ASCRS 2012.