Background and Objective: Pleural infection is associated with significant mortality and morbidityworldwide, with a steadily increasing incidence. We sought to investigate whether video-assisted thoracicsurgery (VATS) or thoracotomy provides the best outcomes in the treatment of stage II and III pleuralinfection as indications remain controversial.Methods: Systematic review of relevant articles from the PubMed database.Key Content and Findings: Nine non-randomized retrospective studies published between 1996and 2020 with a total of 2,121 patients were included. Results varied between studies, but overall shorteroperative and recovery times and greater patient satisfaction were demonstrated using VATS compared withthoracotomy.Conclusions: Although VATS and thoracotomy are viable treatment options for stage II and III pleuralinfection, VATS has potential advantages in terms of decreased operation time, fewer days with tubedrainage, shorter postoperative hospital stay, reduced postoperative pain, increased patient satisfactionwith the procedure, and wound appearance. VATS has limitations in the treatment of patients with stageIII pleural infection, where delayed surgical referral has been shown to increase the risk of intraoperativeconversion to thoracotomy. The data to date implies that debridement by VATS should be proposed as soonas possible in stage II pleural infection and considered in cases of stage