Background: To minimize the risks of barotrauma during nonintubated thoracoscopic-surgery under spontaneous ventilation, we investigated an adjuvant transthoracic negative-pressure ventilation (NPV) method in patients operated on due to severe emphysema or interstitial lung disease. Methods: In this retrospective study, NPV was employed for temporary low oxygen saturation and to achieve end-operative lung re-expansion during nonintubated lung volume reduction surgery (LVRS) for severe emphysema (30 patients, LVRS group) and in the nonintubated wedge resection of undetermined interstitial lung disease (30 patients, wedge-group). The results were compared following 1:1 propensity score matching with equivalent control groups undergoing the same procedures under spontaneous ventilation, with adjuvant positive-pressure ventilation (PPV) performed on-demand through the laryngeal mask. The primary outcomes were changes (preoperative–postoperative value) in the arterial oxygen tension/fraction of the inspired oxygen ratio (ΔPO2/FiO2;) and ΔPaCO2, and lung expansion completeness on a 24 h postoperative chest radiograph (CXR-score, 2: full or 1: incomplete). Results: Intergroup comparisons (NPV vs. PPV) showed no differences in demographic and pulmonary function. NPV could be accomplished in all instances with no conversion to general anesthesia with intubation. In the LVRS group, NPV improved ΔPO2/FiO2(9.3 ± 16 vs. 25.3 ± 30.5,p= 0.027) and ΔPaCO2(−2.2 ± 3.15 mmHg vs. 0.03 ± 0.18 mmHg,p= 0.008) with no difference in the CXR score, whereas in the wedge group, both ΔPO2/FiO2(3.1 ± 8.2 vs. 9.9 ± 13.8,p= 0.035) and the CXR score (1.9 ± 0.3 vs. 1.6 ± 0.5,p= 0.04) were better in the NPV subgroup. There was no mortality and no intergroup difference in morbidity. Conclusions: In this retrospective study, NITS with adjuvant transthoracic NPV resulted in better 24 h oxygenation measures than PPV in both the LVRS and wedge groups, and in better lung expansion according to the CXR score in the wedge group.