Objective: To study the frequency and effect associated with postoperative radiotherapy (RT) for patients with resected gastrointestinal (GI) cancers. Materials and Methods: In observational cohort from the Surveillance, Epidemiology, and End Results (SEER) program, a total of 23,049 patients were identified with resected pancreatic, gastric, esophageal, or rectal carcinomas diagnosed from 1988 to 2003. Using a propensity score analysis, survival differences associated with postoperative RT were analyzed. Results: Adjuvant RT was given to 51.2%, 26.3%, 33.0%, and 58.0% of pancreatic, gastric, esophageal, and rectal cancer patients, respectively. Age and stage of disease were associated with RT use for each site (P<0.001), with younger patients and those with advanced disease receiving RT more frequently. Postoperative RT was associated with a survival benefit for patients with pancreatic cancer (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96), gastric cancer (HR, 0.93; 95% CI, 0.87-0.99), and rectal cancer (HR, 0.84; 95% CI, 0.79-0.90). Subgroups of patients were also identified who experienced the greatest improvement in survival with RT (stage IIB pancreatic cancer, HR=0.71 [95% CI 0.62-0.80]; stage IIIA and IV gastric cancer, HR=0.86 [95% CI 0.77-0.97] and HR=0.77 [95% CI 0.67-0.89], respectively; stages IIA, IIIB, and IIIC rectal cancer, HR=0.87 [95% CI 0.78-0.97], HR=0.71 [95% CI 0.63-0.80], and HR=0.79 [95% CI 0.70-0.90], respectively). Conclusion: Postoperative RT is associated with improved survival for patients who undergo curative resection of pancreatic, gastric, and rectal malignancies. Significant differences are observed for this effect according to stage of disease, with more advanced cases in general experiencing a greater benefit with RT. © 2009 Humana Press Inc.