BACKGROUND A secondary contralateral thoracic surgery is a challenging procedure and is rarely indicated. We retrospectively compared the perioperative values to find out whether video-assisted thoracoscopic surgery under spontaneous ventilation is feasible for this surgery. MATERIAL AND METHODS Patients were retrospectively collected from January 1, 2015 to December 30, 2018 who underwent secondary contralateral video-assisted thoracoscopic surgeries with mechanical ventilation (MV-VATS group) or spontaneous ventilation (SV-VATS group). A propensity score-matching analysis was used to counterbalance the discrepancies. The primary outcome measures were the values of respiratory mechanics and hemodynamics, and the secondary outcome measures were postoperative recovery and complications. RESULTS In the SV-VATS group, the operation and anesthesia times were shorter (P=0.008 and P=0.020, respectively). The peak respiratory pressure value was lower (P<0.001), and there was less use of analgesic drugs during the operation (P<0.001). The vital signs and oxygenation were stable during the operation and in post-anesthesia care unit. The extubation time of laryngeal mask airway, chest-tube duration, and postoperative hospital stay were shorter in the SV-VATS group (P=0.015, P=0.000, P=0.003, respectively), but the duration of intensive care unit stay, the postoperative clinical complications, and chest radiography results were not significantly different between the 2 groups (P>0.05). In the SV-VATS group, postoperative leukocyte count (P<0.001) and neutrophil ratio (P=0.001) were lower and the postoperative value of PaCO2 was slightly higher (P=0.026). CONCLUSIONS VATS under spontaneous ventilation might be an alternative approach for patients who undergo a secondary contralateral thoracic surgery with intraoperative stable vital signs, and does not increase postoperative complications.