Background: There is no randomized prospective evidence to clarify the role of adjuvant radiotherapy in localized colon cancer. Despite this, national consensus guidelines recommend that adjuvant radiotherapy be considered for patients with T4 disease. Given the lack of prospective data, the aim of this study was to evaluate the role of adjuvant radiation therapy (RT) in colon cancer using two large national databases to help to guide treatment decisions. Methods: We evaluated the association of receipt of adjuvant RT with overall survival (OS), using the National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Program (SEER), as well as with disease-specific survival (DSS) using SEER. We analyzed cohorts of patients with histologically confirmed locally advanced T4 adenocarcinoma of the colon, who underwent oncologic surgery with or without adjuvant radiation and had at least 5 years of follow up. For the NCDB cohort, we restricted RT patients to those who received a dose of 45-60 Gy and those who received treatment within 3 months after surgery. We used nearest-neighbor propensity score matching on the basis of age, race, sex, year of diagnosis, grade, N-stage, receipt of chemotherapy, anatomical subsite, margin status, and comorbidity score. To validate our findings, using SEER, we used propensity matching using the same covariates (except comorbidity). Results: After matching of the NCDB cohort, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=1.08; 95% CI 0.89 - 1.30; p=0.448). Using SEER, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=0.9; 95% CI 0.50 - 1.63; p=0.731) or DSS (HR=0.84; 0.54 – 1.33; p=0.46). Conclusions: In summary, after comprehensively adjusting for covariates using two independent national databases, we found no statistically significant association of adjuvant RT with overall- or disease-specific survival for T4 colon cancer. These findings are limited by the retrospective nature of the data and should be tested in a prospective fashion.