The purpose of this article was to assess the benefit of perioperative administration of the intravenous beta-blocker landiolol hydrochloride in preventing atrial fibrillation (AF) after cardiothoracic surgery.We performed a systematic search in PubMed, Web of Science, CNKI, and OVID to identify randomized controlled trials (RCTs) and cohorts up to January 2021. Data regarding postoperative atrial fibrillation (POAF) and safety outcomes were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined using the Mantel-Haenszel method. Meanwhile, subgroup analyses were conducted according to surgery type including lung cancer surgery, esophageal cancer surgery, and cardiac surgery.Seventeen eligible articles involving 1349 patients within 13 RCTs and four cohorts were included in our meta-analysis. Compared with control group, landiolol administration was associated with a significant reduction of the occurrence of AF after cardiothoracic surgery (OR = 0.32, 95% CI 0.23-0.43, P <0.00001). In addition, the results demonstrated that perioperative administration of landiolol hydrochloride minimized the occurrence of postoperative complications (OR = 0.48, 95% CI 0.33-0.70, P = 0.0002). Funnel plots indicated no obvious publication bias.Considering this analysis, landiolol was effective in the prevention of AF after cardiothoracic surgery and did not increase the risk of major postoperative complications.