Background The role of multimodality therapy in stage IIIB non-small cell lung cancer (NSCLC) remains inadequately studied. Although chemoradiation is currently the mainstay of treatment, randomized trials evaluating surgical intervention are lacking, and resection is offered selectively. Methods Data from patients with clinical stage IIIB NSCLC (T4N2 or any N3) undergoing definitive multimodality therapy were obtained from the National Cancer Database (NCDB). Multivariable Cox regression models were fitted to evaluate variables influencing overall survival (OS). Results From 1998 to 2010, 7,459 patients with clinical stage IIIB NSCLC were treated with definitive chemoradiation (CR group), whereas 1,714 patients underwent chemotherapy, radiation, and surgical intervention in any sequence (CRS group). CRS patients were more likely to be younger and white and have slightly smaller tumors (all p < 0.01). There was no difference in Charlson Comorbidity Index (CCI) between the groups (p = 0.5). In the CRS group, 79% of patients received neoadjuvant therapy. Thirty-day surgical mortality was 3%. Factors associated with improved OS in multivariate analysis included younger age, female sex, decreased CCI, smaller tumor size, and surgical resection (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.52-0.63). Among patients treated with surgical intervention, incomplete resection was associated with decreased OS (HR, 1.52; 95% CI, 1.20-1.92). Median OS was longer in the CRS group (25.9 months versus 16.3 months; p < 0.001). Propensity matched analysis on 631 patient pairs treated with CRS versus CR confirmed these findings (median OS, 28.9 versus 17.2 months; p < 0.001). Conclusions Surgical resection as a part of multimodality therapy may be associated with improved OS in highly selected patients with stage IIIB NSCLC. Multidisciplinary evaluation of these patients is critical.