Background <p>By preserving spontaneous breathing and avoiding mechanical ventilation, Non-intubated video-assisted thoracoscopic surgery may attenuate perioperative inflammatory responses and promote early mobilization, thereby influencing the risk of venous thromboembolism. However, whether the risk of postoperative venous thromboembolism differs between Non-intubated video-assisted thoracoscopic surgery and conventional Intubated video-assisted thoracoscopic surgery remains unclear due to a lack of definitive evidence. We hypothesized that patients undergoing Non-intubated video-assisted thoracoscopic surgery would have a lower risk of postoperative venous thromboembolism.</p> Methods <p>A single-center retrospective study was conducted. Patients with lung cancer who underwent video-assisted thoracoscopic lung surgery at the Department of Cardiothoracic Surgery, Jinhua Central Hospital between March 2025 and July 2025 were enrolled and, based on the anesthetic approach, divided into the Non-intubated video-assisted thoracoscopic surgery group (<i>n</i> = 25) and the Intubated video-assisted thoracoscopic surgery group (<i>n</i> = 30). The primary outcome was the risk of venous thromboembolism, as assessed by thrombotic complications, postoperative coagulation parameters, time to early postoperative ambulation, time to first flatus, and time to first defecation.</p> Results <p>No perioperative venous thromboembolic complications occurred in either group. Regarding coagulation parameters, the D-dimer level in the Non-intubated video-assisted thoracoscopic surgery group was 0.30 (0.04, 0.70) µg/L, which was significantly lower than 0.77 (0.34, 1.46) µg/L in the I-VATS group (<i>P</i> = 0.006). There were no statistically significant differences in prothrombin time (PT) or activated partial thromboplastin time (APTT) between the two groups (<i>P</i> &gt; 0.05). The time to early postoperative ambulation was significantly shorter in the Non-intubated video-assisted thoracoscopic surgery group [0 (0, 0) days] than in the Intubated video-assisted thoracoscopic surgery group [1 (1, 1) days] (<i>P</i> &lt; 0.001). The time to first flatus and defecation was 1 (1, 1) day in the Non-intubated video-assisted thoracoscopic surgery group, significantly shorter than 2 (2, 3) days in the Intubated video-assisted thoracoscopic surgery group (<i>P</i> &lt; 0.001). Furthermore, the Non-intubated video-assisted thoracoscopic surgery group exhibited a significantly attenuated elevation in the inflammatory marker (leukocyte count: 2.24 ± 0.39 × 10⁹/L) compared with the Intubated video-assisted thoracoscopic surgery group (5.82 ± 0.60 × 10⁹/L).</p> Conclusions <p>Non-intubated video-assisted thoracoscopic surgery may reduce the risk of venous thromboembolism through several mechanisms: maintaining negative intrathoracic pressure generated by spontaneous breathing, lowering the risk of elevated intra-abdominal pressure, and facilitating early mobilization — all of which enhance venous return; substituting general anesthesia with combined regional anesthesia; and avoiding muscle relaxants, thereby attenuating surgery-induced hypercoagulability and preserving endothelial function.</p>