Purpose: To assess results with twice-daily high-dose radiotherapy (RT) for non-small-cell lung cancer (NSCLC). Patients and Methods: Between 1991 and 1998,94 patients with unresectable NSCLC were prescribed greater than or equal to 73.6 Gy via accelerated fractionation. Fifty were on a phase II protocol (9 group); 44 were similarly created off-protocol (NP group). The clinical target volume received 45 Gy at 1.25 Gy bid (6-hour interval), The gross target volume received 1.6 Gy bid to 73.6 to 80 Gy over 4.5 to 5 weeks using a concurrent boast technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated by the Kaplan-Meier method. Median follow-vp durations for surviving P and NP patients were 67 and 16 months, respectively. Results: Total doses received were greater than or equal to 72 Gy in 97% of patients. The median OS by stage wets 34, 13, and 12 months for stages I/II, IIIa, and IIIb, respectively. LPFS was significantly longer for patients with T1 lesions (median, 43 months) versus T2-4 (median, 7 to 10 months; P = .01). Results were similar in the P and NP groups. Acute grade greater than or equal to 3 toxicity included esophagus (14 patients; 15%), lung (three patients; 3% [one grade 5]), and skin (four patients; 4%). Grade greater than or equal to 3 late toxicity in 86 assessable patients included esophagus (three patients; 3%), lung (15 patients; 77% [three grade 5]), skin (five patients; 6%), heart (two patients; 2%), and nerve (one patient; 1%). Conclusion: This regimen yielded favorable survival results, particularly for T1 lesions. Acute grade greater than or equal to 3 toxicity seems greater than for conventional RT, though most patients recovered. Late grade greater than or equal to 3 pulmonary toxicity occurred in 17%. Because of continued locoregional recurrences, we are currently using doses greater than or equal to 86 Gy. (C) 2001 by American Society of Clinical Oncology.