Background: Radiation induced lung injury is an ominous adverse reaction in the management of thoracic disease by radiation therapy. Although the importance of the area of irradiated lung is well known, the irradiated area of mediastinum is little to be considered in the routine treatment. Purpose: To evaluate the significance of the irradiated area of the mediastinum in the simulation film for radiation induced lung injury. Patients and Methods: A total of 208 patients with primary lung cancer treated with radiation therapy were analyzed for incidence of radiation induced lung injury. Lung injury was defined as the appearance of an abnormal shadow on the chest radiograph. CT images were used to differentiate recurrence or other conditions. Age, sex, irradiation dose, irradiated lung area, T and N factors of the tumor, irradiated mediastinum area, performance status of patients, location of irradiated fields and use of chemotherapy were analyzed with Cox's multivariate regression model. Results: The cumulative rate of radiation induced lung injury at 12 months was 85%. Significant factor of radiation induced lung injury was irradiated area of the mediastinum (p = 0.03). Irradiated area of the lung (p = 0.18, n.s.), total tumor dose (p = 0.1, n.s.), use of chemotherapy (p = 0.08, n.s.) and location of irradiated field (p = 0.08, n.s.) may also have an effect on radiation induced lung injury. Conclusion: The irradiated area of the mediastinum is one of the significant factors in radiation induced lung injury.