PURPOSE: To prospectively assess the feasibility, toxicity, and local control of a class solution protocol of moderately hypofractionated tomotherapy in Stage III, inoperable, locally advanced non-small-cell lung cancer patients. METHODS AND MATERIALS: Eligible patients were treated according to a uniform class solution (70.5 Gy in 30 fractions) with fixed constraints and priorities using helical tomotherapy. Toxicity monitoring was performed using the Radiation Therapy Oncology Group criteria and the National Cancer Institute Common Terminology Criteria and Adverse Events (CTCAE) version 3.0. Pulmonary function tests were performed at the start and repeated at 3 months after treatment. RESULTS: Our class solution resulted in a deliverable plan in all 40 consecutive patients. Acute Grade 3 lung toxicity was seen in 10% of patients. Two patients died during acute follow-up with pulmonary toxicity. Correlations were found between changes in pulmonary function test results and mean lung dose or the lung volume receiving 20 Gy (V(20)). The correlation was strongest for lung diffusion capacity for carbon monoxide. A V(20) of >27% and >32% were predictive for Grades 2 and 3 acute lung toxicity respectively (p < 0.05). Late Grade 3 toxicity was exclusively pulmonary, with an incidence of 16%. Overall Grade 3 lung toxicity correlated with a mean lung dose of >18 Gy and a median lung dose of >5 Gy (p < 0.05). Median survival was 17 months, and the 1-year and 2-year local progression-free survivals were 66% and 50%, respectively. CONCLUSION: The current class solution using moderately hypofractionated helical tomotherapy in patients with locally advanced non-small-cell lung cancer is feasible. Toxicity was acceptable and in line with other reports on intensity-modulated radiotherapy. The local progression-free survival was encouraging considering the unselected population.