Background: A feasibility study was performed to examine the safety and activity profile of Endostar in combination with radiotherapy and Paclitaxel/Carboplatin in patients with unresectable non-small cell lung cancer(NSCLC) of stage III. Methods: Patients with unresectable stage III NSCLC will receive thoracic radiation therapy in 2Gy fractions five times weekly to a total dose of 60-66 Gy and concurrent with Endostar 7.5 mg/m² over 3 hours d1-14, paclitaxel 50 mg/m² weekly over 1 hour, carboplatin AUC=2 mg/mL/min over 30 min weekly. Followed by Endostar 7.5 mg/m² d1-14, paclitaxel 175 mg/m² d1 and carboplatin AUC=5 mg/mL/min d1 every 3 weeks for 2 cycles as consolidation treatment. Objective response rate according to the RECIST criteria was recorded and toxicity was evaluated using the NCI Common Toxicity Criteria. Results: 12 eligible patients enrolled in the study received concurrent Endostar, paclitaxel/carboplatin and definitive thoracic radiation therapy (TRT). Three patients were unable to complete the followed consolidation treatment (two because of pulmonary toxicity and one because of progressive disease). 9 patients (75.0%) had a partial response, while 2 patient’s disease remained stable and 1 patient had progression of the disease. The overall response rate (75.0%,95% confidence interval (CI): 51%-97%) didn’t exceed the goal per study design (85.0%), and the study was therefore closed according to the protocol definition. Main toxicity (grade 3 or greater, %): neutropenia 5 (41.7%); thrombocytopenia 2 (16.7%); anaemia 2 (16.7%); nausea/vomiting 1 (8.3%); anorexia 2 (16.7%), dysphagia 2 (16.7%), radiation pneumonitis 4 (33.3%) and fatigue 1 (8.3%). Conclusions: Our results do not support further trials of Endostar in combination with radiochemotherapy in patients with Stage III NSCLC. Endostar likely enhances radiation pneumonitis. The impact of Endostar on survival as a first-line treatment in combination with radiochemotherapy remains to be determined.