Background: Previous studies on the relationship between gastrointestinal (GI) cancer and cholecystectomy remain inconclusive. We aimed to evaluate this relationship, albeit particularly between cholecystectomy and gastric cancer or colorectal cancer (CRC), and the risk factors of cancer among individuals who have undergone cholecystectomy in Korea. Methods: In total, 4,222 patients who underwent laparoscopic or open cholecystectomy at our institution between January 2006 and December 2013 were included. Patients who underwent cholecystectomy for gallbladder cancer or were undergoing surgery for GI, hepatic, or pancreatobiliary cancers were excluded, as were those who developed stomach cancer or CRC within a year of their cholecystectomy. The included patients were followed until July 20, 2020. The standardized incidence ratio (SIR) was used to calculate the relative risk of GI cancer in cholecystectomy patients. Results: The median patient age (n = 3,588) at the time of cholecystectomy was 54.0 (range, 19–95) years, and the male-to-female ratio was 1:1.04. The median follow-up period after cholecystectomy was 15.0 (range, 0–146) months. We found a 108% greater risk of CRC (SIR, 2.08; 95% confidence interval [CI], 1.28–3.17) and 154% increased risk of CRC in females (SIR, 2.54; 95% CI, 1.16–4.84). Based on multivariate analysis, an age of > 60 years was a significant risk factor for GI cancer in cholecystectomy patients. Conclusion Cholecystectomy may increase risk of CRC, especially in females. Age was considered a risk factor of GI cancers in patients with history of cholecystectomy.