Objective: To explore predictive value of serum homocysteine (Hcy) and brain natriuretic peptide (BNP) levels for recurrence of patients with atrial fibrillation (AF) after radiofrequency ablation (RFA). Methods: During the period from January 2016 to October 2018, 95 AF patients who were admitted to cardiology department of the hospital and healthy adults who underwent physical examination during the same period were enrolled as study objects. They were included into AF group and control group, respectively. After admission, all in both groups were tested for serum Hcy and BNP levels. After RFA, AF group underwent 12-month follow-up. The recurrence situation was statistically analyzed. The risk factors of recurrence in AF patients and predictive value of serum Hcy and BNP were analyzed. Results: The levels of serum Hcy and BNP in AF group were significantly higher than those in control group (P<0.05). The postoperative follow-up for AF patients showed that there were 32 cases with recurrence, with recurrence rate of 33.68%. After comparison, proportion of patients with hypertension and diabetes mellitus in recurrence group was significantly higher than that in non-recurrence group (P<0.05), left atrial diameter, levels of serum Hcy and BNP were significantly higher than those in non-recurrence group (P<0.05). Logistic multivariate analysis showed that after correcting other influencing factors, high serum Hcy and BNP levels were independent risk factors of recurrence in AF patients after RFA (P<0.05). The areas under the curve (AUC) of serum Hcy and BNP for predicting recurrence were 0.774 and 0.828, respectively. Their best cut-off values were 25.7 μmol/L and 78.4 pg/mL, respectively. The area under the curve of the two for predicting recurrence was 0.865. Conclusion: Serum Hcy and BNP levels are related to recurrence in AF patients after RFA. Clinically, high-risk recurrence populations can be screened out based on cut-off values for disease detection and early intervention.