Background: Resection of T4 colon cancer remains challenging compared to lower T stages. Data on the effect of neoadjuvant radiation to improve resectability and survival are lacking. The purpose of this study is to describe the use and outcomes of neoadjuvant radiation therapy in clinical T4 colon cancer. Methods: Adults with clinical evidence of T4 locally advanced colon cancer were included from the National Cancer Database (2004–2014). Bivariate and multivariable analyses were used to examine the association between neoadjuvant radiation therapy and R 0 resection rate, multivisceral resection, and overall survival. Results: Fifteen thousand two hundred and seven patients with clinical T4 disease who underwent resection were identified over the study period. One hundred ninety-five (1.3%) underwent neoadjuvant radiation therapy. Factors associated with the use of neoadjuvant radiation therapy included younger age, male sex, private insurance, lower Charlson Comorbidity Index score, and treatment at an academic research program. Neoadjuvant radiation therapy was associated with superior R 0 resection rates (87.2% neoadjuvant radiation therapy vs 79.8% no neoadjuvant radiation therapy; P =.009). Five-year overall survival was increased in the neoadjuvant radiation therapy group (62.0% neoadjuvant radiation therapy vs 45.7% no neoadjuvant radiation therapy; P <.001). The benefit of neoadjuvant radiation therapy persisted in a Cox proportional hazards multivariable model containing a number of confounding variables, including comorbidity and postoperative chemotherapy (odds ratio 1.37; 95% confidence interval 1.05–1.77; P =.01). In a subgroup analysis of T4b patients, there was an even greater size effect in adjusted overall survival (odds ratio 1.71; 95% confidence interval 1.07–2.72; P =.02). Conclusion: Although radiation is rarely used in locally advanced colon cancer, this National Cancer Database analysis suggests that the use of neoadjuvant radiation for clinical T4 disease may be associated with superior R 0 resection rates and improved overall survival. Patients with clinical T4b disease may benefit the most from treatment. Neoadjuvant radiation therapy should be considered on a case-by-case basis in locally advanced colon cancer.