Background: To investigate whether tubeless uniportal thoracoscopic wedge resection has better short-term outcomes than non-intubated approach with chest tube drainage.Methods: Data were collected retrospectively from January 2017 and December 2019. Tubeless group included 55 patients with pulmonary nodules underwent tubeless uniportal thoracoscopic wedge resection, 211 patients underwent non-intubated uniportal thoracoscopic wedge resection with chest tube drainage were included in drainage group. Perioperative outcomes between two groups were compared. Results: After 1:1 matching, 110 patients remained for analysis, baseline demographic and clinical variables were comparable between the two groups. Mean incision size was 3 cm in both group. Mean operative time was 59.3 minutes in tubeless group and 52.8 minutes in drainage group. The detectable mean lowest SpO2 and mean peak EtCO2 during operation was acceptable in both groups. Conversion to intubated ventilation or thoracotomy was not required. No patient failed the air leak test and did not undergo a tubeless procedure. Mean postoperative hospital stay was 1.5 days in tubeless group and 2.5 days in drainage group. Residual pneumothorax or subcutaneous emphysema was not frequent and mild in tubeless group. The postoperative pain VAS score was pain score was significantly lower in tubeless group in post-operative day 1 and 3. Side effects were rare and mild, including cough and hemoptysis. No reintervention or readmission occurred.Conclusions: Tubeless uniportal thoracoscopic wedge resection with modified air leak test and chest tube drainage is feasible and safe for selected patients with peripheral pulmonary nodules, it might reduce post-operation pain and lead to faster recovery.