General anesthesia providing one-lung ventilation (OLV) with double-lumen endotracheal intubation has been considered inevitable for thoracic surgery. However, with the recent trend of less invasive surgical technique and enhanced recovery after surgery, tubeless anesthesia has been performed in various thoracic surgeries. The aim of this study was to establish a feasible and safe strategy of ventilator-assisted tubeless anesthesia in video-assisted thoracoscopic surgeries (VATS) based on single-institution experiences. We retrospectively reviewed the medical records of patients who underwent tubeless VATS from November 2019 to December 2021. Perioperative anesthetic and surgical variables as well as complications were reported. Seventeen patients with a median age of 29 and American Society of Anesthesiologists physical status I to II underwent video-assisted pulmonary wedge resection under monitored anesthesia care (MAC) using propofol and remifentanil. Mechanical ventilation was applied in synchronized intermittent mandatory ventilation with pressure support mode through facemask if respiratory support was required. During the operation, none of the patients showed hypoxemia or involuntary movement interfering operation. No patients were converted to general anesthesia or open thoracotomy unintentionally. All patients were discharged on median 2 days postoperatively without complications. Ventilator-assisted tubeless VATS is a feasible and safe option in low-risk patients undergoing video-assisted pulmonary wedge resection.