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Purpose: An association between atrial fibrillation (AF) and gastroesophageal reflux disease (GERD) and/or irritable bowel syndrome (IBS) is increasingly being identified; yet the role of radiofrequency catheter ablation (RFA) of AF has not been systematically evaluated in these patient populations., Methods: We performed a prospective matched case-control study of AF patients with GERD and/or IBS who underwent RFA for AF in two centers in North America. AF patients with GERD and/or IBS (gastrointestinal [GI] group) were matched by age, gender, and type of AF at each of the centers with an equal number of AF patients without GERD or IBS (non-GI group)., Results: Sixty patients were included in the study with 30 in each group. Mean age of the population was 45 years with 14 (47 %) males and 21 (87 %) patients with paroxysmal AF in each group. More patients in the GI group had identifiable GI triggers for AF episodes. During RFA, more patients in the GI group had a "vagal response" compared to non-GI group (60 vs 13 %; p < 0.001). Left atrial scar as identified by electroanatomical mapping was more common in patients in the non-GI group compared to the GI group (57 vs 27 %; p = 0.018). At 1-year follow-up, 56 (93 %) of the patients were free from AF with no difference between both groups., Conclusions: Majority of AF patients with GERD and/or IBS have triggered AF and a positive vagal response during RFA. RFA is equally effective in this patient population when compared to those without GERD or IBS.