Background: Empyema is a well-known complication of pneumonia, with high morbidity and mortality rates. This warrants direct treatment either with antibiotics and chest tube drainage or surgery. With less invasive surgical approaches such as uniportal video-assisted thoracoscopic surgery (uVATS), surgical intervention gets a more prominent role early on in the treatment of empyema. The aim of this study was to compare uVATS with the complete VATS (cVATS) approach in empyema, with respect to postoperative complications, hospital length of stay and mortality.Methods: All cases of empyema that were treated surgically in our hospital between 2006 and 2019 were included in a retrospective database. The preferential surgical approach changed from cVATS from 2006 to 2015, towards uVATS from 2016 and on, based on the experience of the surgical team. The database included pre-and postoperative data, as well as peropartive characteristics.Results: One hundred and thirty-seven patients were treated with cVATS and 49 with uVATS. Apart from a slightly reduced kidney function in the uVATS group (57.3±6.3 vs. 71.4±17.2 mL/min/1.73 m 2 , P≤0.001), there were no significant baseline differences in patient characteristics. The duration of uVATS was comparable to cVATS (70±17 vs. 56±23 min, P=0.240), and with low per-and postoperative complications.The postoperative hospital stay was equal in both groups (19±13 vs. 20±15 days, P=0.320). There were no statistically significant differences in postoperative complications or death.Conclusions: Uniportal VATS is a feasible and safe technique for the use in patients with empyema requiring surgery. Even if decortication in stage III empyema is required this can be performed by uniportal VATS.