This prospective randomized trial was performed to determine whether postoperative chemotherapy with vindesine and cisplatin could lengthen time to progression and overall survival in stage III (T1-3N2M0) non-small cell lung cancer (NSCLC) patients. Seventy-two patients were entered; 36 were randomized to receive chemotherapy. Patients were stratified by extent of resection (complete vs. incomplete) and histology (squamous vs. nonsquamous). All had surgery and mediastinal irradiation 6-7 weeks post-thoracotomy. Incompletely resected patients had intraoperative 125I and/or 192Ir implantation. Vindesine (3 mg/m2) weekly x 5, then every 2 weeks x 8, and cisplatin (120 mg/m2) days 1, 29, 71, 113 were planned for those randomized to chemotherapy. No difference in time to progression (median 9.2 months for radiation + chemotherapy vs. 9.0 months for radiation, P = 0.35) or overall survival (16.3 months for radiation + chemotherapy vs. 19.1 months for radiation, P = 0.42) was found. Postoperative vindesine and cisplatin did not prolong time to progression or survival in this population of stage III NSCLC.