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Electrical cardioversion is the most effective and safe method to restore sinus rhythm in patients with persistent AF. However, at least 25% of electrical cardioversions are unsuccessful. The aim of the present study was to evaluate, in a prospective, randomized and double-blind study, the efficacy of a pretreatment with intravenous flecainide in patients who underwent electrical cardioversion. Fifty-four consecutive patients with persistent AF, mean arrhythmia duration 8 (mean 3–18) weeks, were randomized in two groups. In the first group (n = 26), patients received flecainide (2 mg/kg as a 30-minute IV infusion) before electrical cardioversion. In the second group (n = 28), 100 mL IV infusion of 5% glucose was administered 30 minutes before electrical cardioversion. The study evaluated the (1) acute efficacy of electrical cardioversion, (2) mean and maximal energy required, (3) mean number of shocks needed, and (4) incidence of complications. The two groups were similar in terms of age, sex, mean AF duration, left ventricular systolic function, atrial dimension, and cardiovascular risk factors. Seventy-seven percent of patients recovered sinus rhythm with electrical cardioversion. No statistical difference was noted between the two groups: flecainide 19/26 (73%) versus placebo 23/28 (82%). No significant differences were found concerning mean or maximal energy and number of shocks required. No major complications were observed. After a 30-day follow-up, 54% of patients maintained sinus rhythm with no difference between the two groups. Pretreatment with intravenous flecainide before electrical cardioversion is not useful in reducing technical failure of cardioversion, however, flecainide does not diminish the effectiveness of electrical cardioversion.