Objectives:Biochemical studies suggest that patients who have had a colectomy or restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are at an increased risk of developing gallstone disease, but epidemiological studies are lacking. We evaluated the risk of gallstone disease following colectomy and IPAA.Methods:Individuals who had a colectomy were identified from a national cohort of patients with ulcerative colitis (UC), and controls without colectomy were sampled from within the same cohort, matching on gender, calendar year, and year of birth. We used Cox regression to examine the effect of colectomy on the hazard rates of gallstone disease and cholecystectomy, adjusting for alcoholism, stroke, chronic obstructive pulmonary disease, cancer, cardiac disease, diabetes mellitus, hypothyroidism, hyperlipidemia, cirrhosis, obesity, renal failure, and transient ischemic attacks. The effect of an IPAA was determined for patients who had colectomy by including the procedure as a time-dependent variable.Results:We identified 4548 patients and matched these to 44 372 controls without colectomy. During a median follow-up of 11.9 years, 1963 patients were hospitalized for gallstone disease. Patients who had a colectomy were at an increased risk (adjusted hazard ratio (HR)=1.63 (1.39-1.91)), and sensitivity analyses of the risk of undergoing cholecystectomy revealed a similar association (adjusted HR=1.55 (1.22-1.98)). An IPAA did not affect the risk of developing gallstones among patients who had a colectomy (adjusted HR=1.03 (0.77-1.37)).Conclusion:The risk of gallstone disease increases following colectomy for UC.