Objective: To evaluate the effects of low tidal volume combined with different positive end-expiratory pressure (PEEP) on intraoperative ventilation and postoperative pulmonary complications (PPCs) in patients undergoing thoracoscopic pneumonectomy. Methods: A total of 100 patients who underwent thoracoscopic pneumonectomy in Tangdu Hospital from December 2019 to December 2020 were randomly divided into two groups: low PEEP group (group LP) and high level PEEP group (group HP); LP group was set with tidal volume (V_T) 6 mL/kg and PEEP ≤5 cmH₂O during one lung ventilation (OLV), while HP group was set with V_T 6 mL/kg and PEEP 6~10 cmH₂O. Blood gas analysis was performed by radial artery blood before OLV (T1), at OLV 60 min (T2), and at the end of operation (T3). Heart rate (HR), pulse oxygen saturation (SpO₂), systolic blood pressure/diastolic blood pressure (SBP/DBP), partial pressure of end-expiratory carbon dioxide (P_ETCO₂), V_T, peak pressure (Ppeak), plateau pressure (Pplat) of T1, T2 and T3 were recorded. PPCs within 7 days after the operation, removal time of thoracic drainage tube, drainage volume of thoracic drainage tube within 3 days after the operation and postoperative hospital stay were recorded. Results: Compared with T1, there was no significant change in HR at T2 and T3. At T2, mean arterial pressure (MAP) decreased significantly (P<0.05). In both groups, Ppeak and Pplat were significantly increased, while dynamic compliance (Cdyn) was significantly decreased (P<0.05). Oxygenation index (OI) was significantly decreased and alveolar gas-arterial oxygen partial pressure difference (A-aDO₂) was significantly increased in both groups. At T2, respiratory index (RI) was significantly increased in both groups, while at T3, RI was significantly increased in LP group (P<0.05). Compared with LP group, Ppeak of HP group was significantly increased at T2. At T2 and T3, Pplat, driving pressure (DP) and Cdyn in HP group were significantly increased (P<0.05). At T2 and T3, OI and A-aDO₂ and RI in HP group were significantly increased, while A-aDO₂ and RI were significantly decreased (P<0.05). There was no significant difference in PPCs and length of stay between the two groups within 7 days after surgery. Conclusion: Low V_T 6 mL/kg combined with higher PEEP 6–10 cmH₂O can improve aeration and oxygenation during OLV in patients undergoing thoracoscopic pneumonectomy, which is beneficial for anesthesia management.