Background: Drugs are the first choice of treatment for atrial fibrillation (AF), but there is currently a lack of efficient drug treatment options. The aim of this study was to investigate a combination drug treatment plan which may serve as a reference for the treatment of AF. Methods: A total of 316 AF patients admitted to Jiaozhou Central Hospital in Qingdao from October 2020 to October 2022 were selected for this retrospective study. They were divided into a control group (CG, metoprolol, n = 156) and an observation group (OG, moracizine combined with metoprolol, n = 160) based on the treatment they received. The CG and OG groups were compared for clinical efficacy, occurrence of AF, cardiac output (CO), cardiac indexes (CI), stroke volume (SV), stroke indexes (SI) and improvement in QOL. Results: The OG had a better effective rate of treatment, higher levels of CO, CI, SV and SI, and higher QOL scores compared to the CG, as well as a lower AF recurrence rate and AF burden (all p < 0.05). Conclusion: Moracizine combined with metoprolol is an effective treatment for AF patients. This drug combination was found to reduce the AF recurrence rate and burden in AF patients, and to improve their hemodynamic indices and QOL.