Abstract: Objective To compare the clinical efficacy of video-assisted thoracoscopic surgery (VATS) and thoracotomy in the diagnosis and treatment of pulmonary nodules, and evaluate the clinical feasibility and application value of VATS. Methods We collected 50 patients with pulmonary nodules from January 2015 to May 2018. The patients with obvious signs of malignancy by preoperative imaging findings or required surgery, without surgical contraindications, were recruited and divided them into two groups according to the patients' wishes. They were informed about the risks and benefits from different surgical methods before surgery. Twenty-five cases underwent traditional open access, and other 25 cases underwent VATS. In VATS group, one patient was with low lung function and other one was with advanced age. In the VATS group, the "single-hole method", "two-hole method" and "three-hole method" were selected according to the location of the pulmonary nodules and the nature of intraoperative freezing. Data analysis was performed using SPSS 18.0 statistical software. The measurement data were expressed by (ｘ±s), and the count data were analyzed by χ² test. The operation time, intraoperative blood loss, chest tube indwelling time, postoperative hospital stay, etc. were compared between the two groups. Results The relevant observation indexes of VATS group vs thoracotomy group were as follows: operation time: (116.12±46.28) min vs. (142.96±46.27) min, intraoperative blood loss: (55.80±54.86) mL vs. (172.4±102.48) mL, indwelling time of chest tube: (3.40±0.65) d vs. (4.28 ±0.46) d, postoperative hospital stay: (6.12 ±4.28) d vs. (7.92 ±1.66) d, the index of the VATS group was significantly lower than those in the thoracotomy group, and the difference was statistically significant (P<0.05). Conclusion VATS has the advantages of quick recovery, less complications and high safety when compare with traditional open thoracotomy. It is helpful for clear diagnosis, early detection of cancer, improvement of surgical resection rate and improvement of cure rate. So it has positive clinical significance.