Background and Objective: Pleural infection is associated with significant mortality and morbidity worldwide, with a steadily increasing incidence. We sought to investigate whether video-assisted thoracic surgery (VATS) or thoracotomy provides the best outcomes in the treatment of stage II and III pleural infection 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 1996 and 2020 with a total of 2,121 patients were included. Results varied between studies, but overall shorter operative and recovery times and greater patient satisfaction were demonstrated using VATS compared with thoracotomy. Conclusions: Although VATS and thoracotomy are viable treatment options for stage II and III pleural infection, VATS has potential advantages in terms of decreased operation time, fewer days with tube drainage, shorter postoperative hospital stay, reduced postoperative pain, increased patient satisfaction with the procedure, and wound appearance. VATS has limitations in the treatment of patients with stage III pleural infection, where delayed surgical referral has been shown to increase the risk of intraoperative conversion to thoracotomy. The data to date implies that debridement by VATS should be proposed as soon as possible in stage II pleural infection and considered in cases of stage III pleural infection.