: Esophagectomy for esophageal cancer is one of the most invasive gastrointestinal surgeries. In 1996, we introduced video-assisted thoracic surgery for esophageal cancer VATS-E to reduce surgical stress. In 2010, we started employing arti cial pneumothorax AP using carbon dioxide gas in VATS-E to further reduce surgical stress. In this study, we evaluated interleukin-6 IL-6 levels in pleural cavity lavage uid PLF of patients undergoing VATS-E with or without AP, and examined the effect of AP on VATS-E-induced stress. This nonrandomized study included patients who underwent VATS-E with or without AP at Showa University Hospital between 2009 and 2013 and from whom PLF could be collected. IL-6 concentrations in PLF were examined before and after the thoracic part of the operation. We compared IL-6 variation, de ned as the difference between IL-6 concentrations in PLF before and after the thoracic part of the operation, between patients for whom AP was used and those for whom it was not used. A total of 52 patients were included in the study ; 26 underwent VATS-E with AP group AP , and 26 underwent VATS-E without AP group NP . IL-6 concentrations in PLF were significantly elevated immediately after the thoracic part of the operation in both groups. IL-6 variation in PLF correlated with both thoracic operative time and blood loss, which were considered practical parameters of surgical stress, and was signi cantly lower in group AP than in group NP. In conclusion, IL-6 variation in PLF is a useful and sensitive maker of surgical stress during VATS-E. VATS-E with AP is less invasive than VATS-E without AP because AP lowers the perioperative systemic inflammatory response to thoracic surgery.