Although oral amiodarone (AMD) has been used for the management of atrial fibrillation (AF), serious complications such as interstitial pneumonia (IP) occur very occasionally. We evaluated which factors were associated with the development of IP under the long-term administration of AMD in patients with refractory AF.This study included 122 consecutive patients (65.8 ± 11.4 years, mean body mass index [BMI] of 23.2 ± 4.3 kg/m(2)) who orally received AMD to inhibit AF between January 2004 and December 2013. Administration of AMD was begun at 400 mg daily as a loading dose, and was continued at a dosage of 50-400 mg daily after the initial loading phase, determined by the control of the arrhythmias and occurrence of side-effects. The clinical factors were compared between the patients with and without adverse effects, especially IP.During an average follow-up period of 49.2 ± 28.2 months, 53 patients (43.4%) were determined to have converted and maintained sinus rhythm. In contrast, adverse effects were detected in 46 patients (37.7%) with AMD. IP occurred in 8 patients (6.6%), thyrotoxicosis in 35 (28.7%), and others in 5 (4.1%). Four (50.0%) out of 8 patients complicated with IP had obesity (BMI > 27 kg/m(2)). Among the clinical factors, only obesity was significantly associated with the development of IP (P = 0.026).In patients with refractory AF, AMD had an antiarrhythmic effect with long-term administration, but greater adverse effects were also observed. Obesity was the most significant factor associated with the development of IP.