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Purpose: To evaluate alterations in pulmonary function indices after helical tomotherapy and explore potential associations with biologically corrected dosimetric parameters. Patients and methods: In 64 patients with inoperable locally advanced non-small cell lung cancer, pulmonary function tests before and within 6 months after radiotherapy were evaluated retrospectively. In the case of concurrent chemotherapy a total dose of 67.2 Gy was delivered, otherwise 70.5 Gy was provided. In 44 patients, late pulmonary function changes (≥6 months after radiotherapy) could also be assessed. Results: In the entire patient group, there were significant declines in forced expiratory volume in 1s (FEV1) (average change −4.1% predicted; P = 0.007), in forced vital capacity (FVC) (−4.9% predicted; P = 0.002), total lung capacity (TLC) (−5.8% predicted; P = 0.0016) and DLCO (diffusing capacity of the lung for carbon monoxide corrected for hemoglobin level) (−8.6% predicted; P < 0.001) during the first 6 months. CorrespondingFEV1, FVC, TLC and DLCO declines in the subgroup with late measurements (after 11.3 months on average) were −5.7, −7.4, −7.0, −9.8% predicted. A multivariate analysis including V5 Gy, V10 Gy, V20 Gy, V40 Gy, V60 Gy, mean lung dose (MLD), gross tumor volume (GTV) and planning target volume (PTV) as potential covariates showed that GTV was the most consistent contributor, being significant for ∆FEV1 (P = 0.003), ∆FVC (P = 0.003), ∆TLC (P = 0.001) and ∆DLCO (P = 0.01). V5 Gy or V10 Gy did not contribute to any of the lung function changes. Conclusions: The decline in pulmonary function indices after helical tomotherapy was of similar magnitude to that observed in studies reporting the effect of conformal radiotherapy on lung function. Diffusion capacity was the parameter showing the largest decrease following radiation therapy as compared to baseline and correlated with gross tumor volume. None of the alterations in pulmonary function tests were associated with the lung volume receiving low-dose radiation.