Objectives: Postoperative atrial fibrillation (POAF) is a common problem of cardiac surgery. Beta-blockers are recognized as effective prophylactic agents available for POAF management. To better understand its effect on isolated atrial fibrillation after cardiac surgery, a meta-analysis was conducted. Methods: Randomized controlled trials (RCTs) were searched and filtered by comparing the efficacy of beta-blockers and control users in isolated POAF for cardiac surgery. Seventeen RCTs were identified and analyzed by typical meta-analysis methods. The search was performed from inception to May 31, 2020. Subgroup analyses were conducted for type of surgery and beta-blocker, starting time and route of administration of beta-blocker, and dosage of intravenous landiolol hydrochloride. Results: Beta-blockers were effective in reducing isolated POAF risk (risk ratio [RR], 0.52 [0.41, 0.66], P ¼ .31, I 2 ¼ 12%). In subgroup analyses, beta-blocker administration during postoperative period (RR, 0.43 [0.29, 0.62], P ¼ .84, I 2 ¼ 0%) and on-pump coronary artery bypass graft (RR, 0.34 [0.04, 3.15], P ¼ .56, I 2 ¼ 0%) had lowest risk of isolated POAF incidence. Intravenous landiolol hydrochloride at 2 mg/ kg/min also had low risk of isolated POAF occurrence. Conclusions: Beta-blocker treatment helps to reduce isolated atrial fibrillation incidence after cardiac surgery. Our subgroup analyses also reveal postoperative betablocker administration after on-pump coronary artery bypass graft surgery is most effective in reducing isolated POAF risk. Intravenous landiolol hydrochloride at a dosage of 2 mg/kg/min has also displayed favorable results. Further trials may be required to explore these factors.