Abstract: Objective To investigate plasma levels of miR-21, miR-133, miR-328 in patients with atrial fibrillation, and explore their correlation with the recurrence of atrial fibrillation after radiofrequency ablation. Methods Total 500 patients with atrial fibrillation admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University, General Hospital of Shenma Group, the Second Hospital of Shandong University and the Affiliated Hospital of Qingdao University from September 2016 to September 2018 were selected as the study objects, and 200 healthy patients who underwent physical examination in Beijing Anzhen hospital during the same period were selected as the control group. Fasting venous blood was extracted to detect the levels of miR-21, miR-133 and miR-328. All patients with atrial fibrillation were treated with radiofrequency ablation. After the operation, oral propafenon 150 mg was taken 3 times/d for 1 month, and the patients were followed up for 1 year. MicroRNA expression levels of patients in recurrent group and the non-recurrent group were compared, and the effect of microRNA in predicting the recurrence of atrial fibrillation was analyzed. Results Postoperative recurrence occurred in 136 of the 500 patients with atrial fibrillation(27.2%). There was no significant difference in baseline data among the three groups(all P<0.05).The expressions of miR-21 and miR-328 in the recurrent group and the non-recurrent group were higher than those in the control group, while the expressions of miR-133 were lower than those in the control group(all P<0.05). However, only miR-21 in the recurrence group and the non-recurrence group showed statistical significance(P<0.05).The ROC curve for predicting the recurrence of atrial fibrillation showed that miR-21 cut-off value(1.995) had the highest diagnostic efficiency, with sensitivity, specificity, Youden index and AUC of 77.21%, 83.79%, 0.610 and 0.876, respectively. Conclusion The significantly increased expression of miR-21 in plasma is of certain reference value for predicting the recurrence of atrial fibrillation after radiofrequency ablation, it can be used as a basis for guiding clinical treatment.