Background: Non-intubated video-assisted thoracoscopic surgery (NIVATS) is increasingly performed in different types of thoracic procedures. Based on the anesthetic perspective, the outcomes of this method are limited. General anesthesia with intubation and controlled ventilation for video-assisted thoracoscopic surgery (IVATS) is a standard technique. The current study aimed to compare the pulmonary gas exchange between NIVATS and IVATS, with a focus on desaturation event.Methods: This was a retrospective study conducted at Vajira Hospital. Data were collected from the hospital medical record database between January 9, 2019, and May 15, 2020. A propensity score-matched analysis was used to adjust the confounders by indications and contraindication between NIVATS and IVATS. The perioperative outcomes of VATS and NIVATS were compared by the regression analysis method.Results: In total, 180 patients were included in the analysis. There were 98 and 82 patients in the NIVATS and IVATS groups, respectively. After a propensity score matching, the number of patients with similar characteristics decreased to 52 per group. None of the patients in both groups experienced desaturation. The lowest oxygen saturation of the NIVATS and IVATS groups did not significantly differ (96.5% vs. 99%, respectively; p = 0.185). The NIVATS group had a significantly higher ETco2 peak than the IVATS group (43 vs. 36 mmHg, respectively; p < 0.001). According to the regression analysis, the NIVATS group had a significantly shorter anesthetic induction time (Mean difference (MD) = -5.135 min (95 % CI = (- 8.878)- (-1.391)) and lower volume of blood loss (MD =-75.565 ml (95%CI = (- 131.08) - (- 20.65) but a higher intraoperative ETCO2 than the IVATS group (MD = 4.561 mmHg (95%CI=1.852 - 7.269). Four patients in the NIVATS group required conversion to intubation due to difficulties encountered when using the surgical technique (7.7%, p = 0.041). Seven patients in the IVATS group, but none in the NIVATS group, presented with sore throat (13.5% vs. 0%, respectively; p = 0.006). Moreover, none of the patients in both groups experienced postoperative pneumonia, underwent reoperation, or died.Conclusions: The anesthetic and surgical outcomes of NIVATS were comparable to those of IVATS.