Abstract: AIM:To introduce treatment strategies and analyze their therapeutic effect for atrial septal defect (ASD) with atrial fibrillation (AF) in adult patients. METHODS: Twenty-four patients with atrial septal defect with significant clinical symptoms and ineffective drug treatment were analyzed. In the radiofrequency catheter ablation (RFA) group there were four patients who underwent transcatheter closure of ASD and radiofrequency catheter ablation, in the RFA maze group there were 14 patients who underwent ASD repair operation and radiofrequency ablation modified maze procedure with cardiopulmonary bypass, and in the simple interventional closure group there were six cases who underwent only transcatheter closure of ASD and no radiofrequency catheter ablation. Preoperatively and 12 months postoperatively, electrocardiogram and echocardiogram were compared. RESULTS: No serious complications and operative death occurred in the 24 patients under study. In the radiofrequency catheter ablation group, three patients restored to sinus rhythm after a 12-month follow-up and one patient underwent radiofrequency ablation again before restoration to sinus rhythm. In the RFA maze group 11 patients restored to sinus rhythm after the same 12-month period, two patients remained in atrial fibrillation and one patient remained in junctional rhythm. The success rate of sinus rhythm was 50% in the simple interventional closure group. Compared with the preoperative measurements, echocardiography showed that right atrium and right ventricular diameter significantly reduced in each group (all P<0.05) and pulmonary artery pressure significantly decreased (all P<0.05), with no significant differences among the three groups. The success rates of sinus rhythm in both radiofrequency catheter ablation group and RFA maze group were higher than in the simple interventional closure group. CONCLUSION: Transcatheter closure and ASD repair surgery are effective and safe for treating secundum-type ASD. Radiofrequency catheter ablation and RFA maze procedure are effective in resolving AF for ASD patients with AF and strengthen heart function. Appropriate selection of the treatment strategy for ASD with AF is the key to surgical success.