Recent studies suggest that radiation therapy (RT) dose escalation in early-stage non-small-cell lung cancer (NSCLC) is feasible when 3-dimensional therapy is used. However, the accompanying prolongation of the treatment course when standard fractionation is used could be suboptimal from a practical and biologic standpoint. We report results of a compressed course of RT for patients with pathologically documented clinical stage 1 NSCLC who were unsuitable for curative surgery because of pulmonary dysfunction or other medical comorbidities. Thirty-one lesions were treated with dose-intensive RT (eg, fraction>or=2.25 Gy and nominal total dose>or=60 Gy) and have been followed up for >or=6 months from the completion of treatment. All patients completed therapy without interruption. Three patients developed grade 3 pulmonary toxicity 1-3 months after therapy. The overall tumor response rate was 88% (35% complete response and 53% partial response), whereas in-field tumor progression was documented for 5 of 31 lesions. Actuarial median survival was 38 months and 3-year overall survival was 60%, and most deaths were secondary to intercurrent disease. Moderately accelerated single daily fractionated RT is feasible for high-risk patients with early-stage NSCLC and merits further investigation.