Combined use of pentoxifylline and vitamin E is reported to reduce radiation-induced toxicity in normal tissues at molecular level. We plan to evaluate the role of combined use of pentoxifylline (PTX) and alpha-tocopherol (vitamin E; Vit E) for minimizing radiation-induced lung toxicity. A total of 91 lung cancer patients were randomized. Among them, 44 received PTX (400 mg three times a day orally and Vit E 300 mg twice a day orally during the entire period of radiotherapy. PTX and Vit E were further administered at doses of 400 mg once a day and 300 mg once a day, respectively for 3 months after radiotherapy. A total of 47 patients were assigned as a control group. Radiation related acute and late toxicities are evaluated by radiation RTOG/EORTC toxicity scale. Median age was 59 (range, 41-75). Median follow-up was 13 months (range, 3-28 months). Radiation-induced lung toxicity was more frequent in control group for all phases than in pentoxifylline and alpha-tocopherol group (acute phase, P = 0.042, subacute phase P = 0.0001, late phase P = 0.256). PTX and Vit E combination might be considered especially in patients with lung cancer who receive concurrent chemo-radiotherapy, or have a poor respiratory function tests.