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ObjectiveThe goal of this study was to explore the feasibility and safety of spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) for non-small-cell lung cancer (NSCLC) patients with poor lung function.MethodsNSCLC patients with poor lung function who underwent SV-VATS or mechanical ventilation VATS (MV-VATS) from 2011 to 2018 were analyzed. 1:2 Propensity score matching (PSM) was applied, and the short- and long-term outcomes between the SV-VATS group and the MV-VATS group were compared.ResultsAnesthesia time (226.18 ± 64.89 min vs. 248.27 ± 76.07 min; P = 0.03), operative time (140.85 ± 76.07 min vs. 163.12 ± 69.37 min; P = 0.01), days of postoperative hospitalization (7.29 ± 3.35 days vs. 8.40 ± 7.89 days; P = 0.04), and days of chest tube use (4.15 ± 2.89 days vs. 5.15 ± 3.54 days; P = 0.01), the number of N1 station lymph node dissection (2.94 ± 3.24 vs. 4.34 ± 4.15; P = 0.005) and systemic immune-inflammation index (3855.43 ± 3618.61 vs. 2908.11 ± 2933.89; P = 0.04) were lower in SV-VATS group. Overall survival and disease-free survival were not significantly different between the two groups (OS: HR 0.66, 95% CI: 0.41–1.07, P = 0.09; DFS: HR 0.78, 95% CI: 0.42–1.45, P = 0.43).ConclusionsComparable short-term and long-term outcomes indicated that SV-VATS is a feasible and safe method and might be an alternative to MV-VATS when managing NSCLC patients with poor lung function.