Atrial fibrillation (AF) is commonly found in patients with structural heart disease (SHD), including atrial septal defect (ASD). The feasibility and safety of ablation for AF in patients with unrepaired ASD is seldom reported. This study aims to evaluate and compare the long-term efficacy of AF ablation in patients with and without ASD. From January 2008 to December 2012, 18 consecutive patients were identified with medically refractory AF and an unrepaired ASD under catheter ablation. For each ASD patient, four control subjects were matched from our database. There were no significant differences between groups in terms of age, sex, type of AF, LA diameter, LVIDD, and EF. The mean procedural and fluoroscopy times were not different between the groups (p = NS). After a median follow-up of 20 months, the patients in the ASD group had 44.4 % AF recurrence after a single procedure compared with 34.7 % in the control group (p = 0.11). The mean LA diameter in non-recurrent patients was smaller than in recurrent patients (p = 0.03). In univariate Cox proportional hazards analyses, the factor found to have a significant association with arrhythmia recurrences was left atrial diameter (hazard ratio 1.059, 95 % confidence interval 1.002 to 1.120, p = 0.03). These results indicate that in patients with AF and an ASD amenable to percutaneous closure, a staged approach with radiofrequency ablation of AF preceding closure is a rational strategy.