Background: The aim of this systematic review and meta-analysis was to determine the efficacy and safety of omitting chest drains compared to routine chest drain placement after video-assisted thoracoscopic surgery (VATS). Methods: Five bibliographic databases, ClinicalTrials.gov and PROSPERO were comprehensively searched from inception to July 29, 2020 (no language restrictions). Postoperative outcomes were extracted and synthesized complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Risk of bias (RoB) including non-reporting bias, heterogeneity, and sensitivity were assessed. Subgroup analyses were performed based on study design. Results: Of 7,166 identified studies, 10 studies [four randomized controlled trials (RCTs) and six non-RCTs] with 1,079 patients were included. There were 561 patients in the no chest drain group (NCD) and 518 patients in the standard chest drain group (CD). In pairwise analysis the NCD group had significant shorter length of stay (LOS) [weighted mean difference (WMD) -1.53 days, P<0.001], less postoperative pain scores (WMD -1.09, P=0.002), but higher risk of drain insertion or thoracocentesis [risk radio (RR) 3.02, P=0.040]. There were no significant differences on the incidence of minor pneumothorax (RR 1.77, P=0.128), minor pleural effusion (RR 1.88, P=0.219), minor subcutaneous emphysema (RR 1.37, P=0.427) or pneumonia (RR 0.53, P=0.549). No mortality was observed in either group during the observation period (in-hospital or 30-day mortality). Conclusions: Omitting chest drains in selected patients after VATS seems effective leading to enhanced recovery with shorter length of postoperative stay and less pain but with a higher risk of drain insertion or thoracocentesis. However, a major part of the evidence comes from observational studies with high RoB. Further RCTs are needed to improve the current evidence.