Background: At present, we have many diagnostic methods, but there are no specific guidelines on the diagnosis and treatment of bilateral multiple pulmonary nodules (BMPNs). Clinically, one-stage video-assisted thoracic surgery (VATS) for BMPNs is not the usual treatment. Methods: We retrospectively analyzed the clinical data of 18 patients with bilateral pulmonary nodules who underwent one-stage VATS from January 2016 to Jun 2018 in the Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, at the Huazhong University of Science & Technology. All patients were suspected of multiple primary lung cancer (MPLC) and underwent diagnostic and therapeutic one-stage VATS. Results: All operations were completed successfully. Duration of chest drain use was 3-15 (5.28 +/- 2.67) days. The overall duration of hospitalization after surgery was 8-19 (12.58 +/- 5.87) days. The incidence of postoperative complications was 16.67% (3 patients in all). The postoperative complications included 1 patient with subcutaneous emphysema, 1 patient with a persistent pulmonary air leak and 1 patient with the development of pleural effusion after removal of the drainage tube. There was no postoperative death. Conclusions: Through rigorous preoperative assessment, it was demonstrated that one-stage VATS is safe and feasible for patients with BMPNs. Patients can avoid progression of the contralateral tumor, the trauma of the second operation, and the various burdens of medical treatment.