Objective <p>Postoperative atrial fibrillation (POAF) remains a common complication after off-pump coronary artery bypass grafting (OPCAB). We evaluated the preventive effect of short-term perioperative landiolol hydrochloride administration on POAF after OPCAB.</p> Methods <p>This single-center retrospective observational study included patients who underwent elective isolated OPCAB between February 2013 and August 2018. Patients with a history of atrial fibrillation, emergency surgery, or conversion to cardiopulmonary bypass were excluded. Landiolol hydrochloride was continuously administered from the beginning of surgery until postoperative day 1. The primary endpoint was POAF occurrence. Secondary endpoints included hospital stay, perioperative complications, and healthcare insurance reimbursement points. Propensity score matching was performed to adjust baseline differences.</p> Results <p>Among eligible patients, 74 were assigned to the control group and 159 to the landiolol group. Propensity score matching generated 68 matched pairs. POAF incidence was significantly lower in the landiolol group in both the unadjusted cohort (15.7% vs. 31.1%, <i>p</i> = 0.01) and propensity score matched cohort (14.7% vs. 32.4%, <i>p</i> = 0.02). No significant differences were observed in hospital stay or major clinical outcomes, including 30-day mortality, stroke, and prolonged intubation. However, medical insurance points were significantly lower in the matched intervention group (258,460 vs. 267,904 points, <i>p</i> = 0.047).</p> Conclusions <p>Short-term perioperative administration of landiolol hydrochloride was associated with a lower incidence of POAF after OPCAB without an increase in perioperative complications. While further prospective randomized studies are needed, this simplified protocol may offer a safe, feasible, and potentially cost-favorable strategy for POAF prevention after cardiac surgery.</p>