Background: Chemoradiation with curative intent is considered standard of care in patients with locally-advanced, stage III non-small cell lung cancer (NSCLC). However, there may be patients with stage III (N2 or N3, including T4) NSCLC who may be eligible for surgery. The objective of this systematic review was to investigate the efficacy of surgery after chemoradiotherapy compared with chemoradiotherapy alone in patients with locally-advanced NSCLC.Methods: MEDLINE, EMBASE, and PubMed were searched for randomized controlled trials (RCTs) comparing surgery after chemoradiotherapy versus chemoradiotherapy alone in patients with stage III (N2 or N3, excluding T4) NSCLC.Results: Three included RCTs consistently found no statistically significant difference in overall survival between patients with locally-advanced NSCLC who received surgery and chemoradiotherapy or chemoradiotherapy alone. Only one RCT found a significantly longer progression-free survival (PFS) in patients treated with chemoradiation and surgery (HR, 0.77; 95% confidence interval [CI], 0.62 to 0.96). In a post-hoc analysis of the same trial, the rate of overall survival was higher in the surgical group compared with patients matched in the chemoradiation-alone group if a lobectomy was performed (p=0.002), but not when a pneumonectomy was performed. Furthermore, fewer treatment-related deaths occurred among patients who received lobectomy compared with pneumonectomy.Conclusion: For patients with locally-advanced NSCLC, the benefits of surgery following chemoradiation were uncertain. Surgery after chemoradiation for patients who do not require a pneumonectomy may be an option.