Background: The role of radiation therapy in addition to chemotherapy has not been well established in non-oligometastatic Stage IV non-small cell lung cancer (NSCLC). We aimed to investigate overall survival (OS) of non-oligometastatic Stage IV NSCLC treated with chemotherapy with concurrent radiation to the primary tumor. Methods: Eligible patients were screened from two prospective studies. Oligometastatic and non-oligometastatic NSCLC were defined as having < 5 and >= 5 metastatic lesions, respectively. Prognostic factors for OS were identified by using univariate and multivariate analysis. Landmark analysis and propensity-score matching (PSM) were each performed to further adjust for confounding. Results: A total of 274 patients were identified as the study cohort: 183 had non-oligometastatic disease. For all 274 patients, those who received a radiation dose >= 63 Gy to the primary tumor and had oligometastatic disease had better OS (P < 0.001 and P = 0.017, respectively). When patients were subdivided into those with oligometastatic or non-oligometastatic disease, a radiation dose = 63 Gy remained a significant prognostic factor for better OS. For non-oligometastatic patients, multivariate analysis showed that receiving = 63 Gy radiation, having a GTV < 146 cm(3), having response to chemotherapy, and having stable or increased post-treatment KPS independently predicted better OS (P = 0.018, P = 0.014, P = 0.014, and P = 0.001). After PSM in non-oligometastatic patients, a higher radiation dose (= 63 Gy) remained to be correlated with better OS. By landmark analysis, aggressive radiation (= 63 Gy) remained to be correlated with better OS in Pre-PSM cohort (P = 0.005) and Post-PSM cohort (P = 0.004). Conclusions: Radiation dose, primary tumor volume, response to chemotherapy and KPS after treatment are associated with OS in patients with non-oligometastatic disease; on basis of effective system chemotherapy, aggressive thoracic radiotherapy may prolong OS.