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Atrial fibrillation (AF) is a difficult arrhythmia to manage with antiarrhythmic agents. Amiodarone is highly effective in restoring and maintaining normal sinus rhythm in patients with AF. However, the mechanism and predictors of efficacy for amiodarone in treating AF have not been adequately addressed. Various measures of success or failure of amiodarone therapy were examined in 68 patients who had paroxysmal or chronic, established AF refractory to conventional antiarrhythmic agents. The patients were 25 to 75 years old (mean 59) and mean follow-up was 21 months (range 3 to 56). Maintenance amiodarone dosages were 200 to 400 mg/day. Overall, amiodarone therapy was effective long term in 54 of the 68 patients (79%). Left atrial diameter, age, gender and origin of AF were not helpful in predicting success or failure of amiodarone therapy. The presence of chronic AF for longer than 1 year was an adverse factor in maintaining normal sinus rhythm (p = 0.007), although the success rate even in this group was relatively high (57%). Thirty-five percent of the patients had adverse effects, which precluded long-term therapy with amiodarone in 10%.