Background: Cisplatin-based chemotherapy and concurrent radiotherapy is the standard treatments for LA-NSCLC. Thistrial evaluated two experimental regimens of chemotherapy with concurrent radiotherapy. Methods: Eligible patients with unresectable stage III NSCLC, 20 to 74 years of age, and ECOG PS of 0–1 were randomized to either Arm SP, S-1 (40 mg/m²/dose per oral, b.i.d, on days 1-14) and cisplatin (60 mg/m² on day 1) repeated every 4 weeks or Arm VP, vinorelbine ( 20mg/m² on day 1, 8) and cisplatin (80 mg/m²on day) repeated every 4 weeks with early concurrent thoracic radiotherapy of 60 Gy at 2 Gy per daily fraction. The primary endpoint was overall survival rate at 2-year (2yr-OS). A pick-the-winner design was used to identify the treatment regimen most likely to be superior. The planned sample size was 55 patients per arm, assuming in each arm that the null hypothesis for 2yr- OS was 50% versus an alternative hypothesis for 65% with one-sided alpha of 0.10 and power of 80% (Study ID: UMIN000002420). Results: One hundred eleven patients were registered between Sep 2009 and Sep 2012. Of 108 patients for efficacy analysis, the 2yr-OS was 76% (95% CI, 62-85%) for SP and 69% (95% CI, 54-79%) for VP. The hazard ratio (HR) of death between the two arms was 0.85 (0.48-1.49). The median progression-free survival (PFS) was 14.8 months for SP and 12.3 months for VP with a HR of 0.92 (0.58-1.44). 80% and 48% of patients completed the protocol treatment in SP and VP, respectively. Common grade 3-4 toxicities in SP v VP were neutropenia 33.3% v 75.9%, platelets 9.3% v 3.7%, hemoglobin 1.9% v 27.8%, febrile neutropenia 9.3% v 16.7%, diarrhea 5.6% v 0%. There were 4 and 5 treatment-related deaths in SP and VP, respectively. Conclusions: Both arms rejected the null hypothesis for 2yr-OS. In this study Arm SP was declared the winner in terms of 2yr-OS, PFS, treatment completion, and toxicity. Clinical trial information: 000002420.