A phase III randomized trial was conducted to investigate whether induction chemotherapy followed by radiation can influence survival as compared with radiation alone in unresectable, locally advanced non-small-cell lung cancer (LADNSCLC). A total of 101 patients with unresectable stage IIIA or IIIB NSCLC were enrolled. Patients were stratified by performance status, weight loss, histology and stage, and then randomized to receive combined chemoradiotherapy or radiotherapy alone. Radiotherapy was administered in 1.8 Gy to 2.0 Gy standard fractions daily 5 times weekly for a total dose of 60 Gy to 65 Gy. The combined group received induction of cisplatin, etoposide, and vinblastine (PEV) chemotherapy with cisplatin 20 mg/m2 on days 1 to 5, etoposide 100 mg/m2 on days 2 to 4, and vinblastine 6 mg/m2 on day 1, which wasrepeated every 3 weeks for 3 courses, after which time the patients underwent radiotherapy. Of 101 patients registered, 89 patients (43 combined, 46 radiotherapy alone) were eligible for analysis. The response rates for the combined and radiotherapy groups were 65% (28/43) and 70% (32/46), respectively. The median survival time (MST) showed a tendency to be more prolonged in the combined group than in the group receiving radiotherapy alone (13.8 vs. 8.5 months). The MST in patients with nonsquamous histology was strikingly prolonged in the combined group as compared with the radiotherapy group (14 vs. 3.6 months, p 0.027). Likewise, the MST in patients with stage IIIB was significantly prolonged in the combined group as compared with the radiotherapy group (11.1 vs. 7.2 months, p 0.045). Together, the MST of the high-risk group with nonsquamous or stage IIIB was significantly higher in the combined group than that seen in the radiotherapy group (11.6 vs. 8 months, p 0.046), whereas the MST of the low-risk group, defined as having both squamous histology and stage IIIA, was similar in the two treatment groups (18.3 vs. 20.8 months, p = 0.293). In conclusion, induction PEV chemotherapy plus radiotherapy is superior to radiotherapy alone in high-risk subsets of unresectable LAD-NSCLC and therapeutic strategy should be based on the identification of prognostic factors.