PURPOSE: To investigate the effect of smoking during radiotherapy (RT), respiratory insufficiency before RT, hemoglobin levels during RT, and additional factors on overall survival, locoregional control (LRC), and metastasis-free survival in non-small-cell lung cancer patients. METHODS AND MATERIALS: The following factors were investigated in 181 patients who underwent RT for non-small-cell lung cancer: age, gender, Karnofsky performance score, histologic type, grade, T/N stage, American Joint Committee on Cancer stage, surgery, chemotherapy, respiratory insufficiency before RT, pack-years, smoking during RT, and hemoglobin levels during RT. Additionally, in the 129 patients who did not undergo surgery, the effect of the equivalent dose in 2-Gy fractions (EQD2) (<60 Gy vs. 60 Gy vs. >60 Gy) on outcome was investigated. RESULTS: On multivariate analysis, improved overall survival was associated with a lower T stage (p = 0.004), lower N stage (p = 0.040), surgery (p = 0.010), and no respiratory insufficiency (p = 0.023). A Karnofsky performance score >70 achieved borderline significance (p = 0.056). Improved LRC was associated with a lower T stage (p = 0.007) and no smoking during RT (p = 0.029). Improved metastasis-free survival was associated with lower T stage (p < 0.001) and lower N stage (p < 0.001). In those patients who did not undergo surgery, an EQD2 of > or =60 Gy was associated with a better outcome than an EQD2 of <60 Gy. Furthermore, an EQD2 >60 Gy resulted in better LRC than did an EQD2 of < or =60 Gy. CONCLUSIONS: Smoking during RT had a significant effect on LRC, but we did not find that hemoglobin levels or respiratory insufficiency significantly affected LRC or metastasis-free survival in our patient population. Furthermore, our data suggest a dose-effect relationship in those patients who did not undergo surgery.