553 Background: The standard treatment for non-metastatic locally advanced (T4M0) non-rectal colon cancer is surgical resection followed by adjuvant chemotherapy. There is strong rational for the use of post-operative radiation therapy (RT) in T4 tumors since negative margins are difficult to obtain. Despite promising single institutional studies, a phase III clinical trial closed early due to poor accrual. The efficacy of adjuvant RT in these patients remains unknown. We hypothesized that patients at lower risk of micro-metastases would benefit most from aggressive local treatment. Methods: Cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Inclusion criteria: T4-anyN-M0 non-rectal colon cancers, diagnosed between 1988 and 2010. Exclusion criteria: rectal tumors and cases lacking staging information. Endpoints: overall survival (OS) and cancer-specific survival. Analyses were based on the Kaplan-Meier method and Cox proportional hazard model. Results: A total of 36,260 patients with T4 colon cancer were identified. Due to changes in the use of systemic adjuvant therapies, an initial analysis was performed to determine effect of adjuvant RT by year of diagnosis. Prior to 2003, adjuvant RT provided no significant improvement in OS. However, between 2003 and 2010, adjuvant RT improved OS by 8 months, from 48 to 56 months (HR: 0.83, p = 0.001). Within this latter period, adjuvant RT improved OS in three subsets of the population: in patients without nodal involvement (N0) (HR: 0.79, p = 0.009); in patients with primary tumor in the sigmoid colon (HR: 0.79, p=0.007); in patients with primary tumor size of 6cm or greater (HR: 0.74, p < 0.001). On multivariate analysis, the following categories remained significant: N stage, tumor grade, year of diagnosis, gender, primary site, and radiation therapy. Conclusions: Some patients with T4 non-rectal colon cancer appear to benefit from adjuvant RT after surgical resection of the primary tumor, especially node-negative tumors located within the sigmoid colon, larger than 6cm in diameter. This benefit has become more evident since the introduction of more effective adjuvant chemotherapy. Our conclusions require verification in a prospective study.