Background Very large, locally advanced non-small cell lung cancers (NSCLC) remain a therapeutic challenge. This retrospective study compares the effect of treatment modalities on survival of patients with large NSCLC with hilar lymph node involvement (T3>7cmN1). Methods The National Cancer Data Base was used to identify adult patients who were diagnosed with T3 >7cmN1 NSCLC from 1999 to 2005 (n = 642). Nonsurgical treatments included chemoradiation, chemotherapy, radiation therapy, or no treatment, whereas primary surgical treatments included surgery, chemoradiation or chemotherapy prior to surgery, chemoradiation or chemotherapy after surgery, or postoperative radiotherapy. Five-year overall survival (OS) was estimated by the Kaplan-Meier method and comparisons made using log-rank tests and Cox regression models. Results A total of 642 patients were evaluated; 425 nonsurgical (66%) and 217 surgical (34%). Primary surgical therapy was associated with improved 5-year OS; 28% versus 8% and 4% for nonsurgical and no treatment, respectively (p < 0.001). The 5-year OS were 11%, 5%, 2%, and 4% for chemoradiation, chemotherapy, radiation therapy, and no treatment, respectively (p < 0.001). The 5-year OS were 16% for surgery only, 40% and 44% for neoadjuvant chemoradiation or chemotherapy with surgery, respectively, 40% and 38% for adjuvant chemoradiation or chemotherapy with surgery, respectively, and 18% for postoperative radiotherapy (p < 0.001). On multivariate analysis, surgery and chemotherapy in most combinations were associated with significantly improved OS compared with chemoradiation only. Conclusions Surgery with systemic therapy delivered in a neoadjuvant or adjuvant fashion for patients with T3>7cmN1 NSCLCs is associated with improvements in OS.