Background- Unlike antiarrhythmic drugs, the safety and beneficial effects of angiotensin II receptor blockade (ARB) in patients with structural heart disease is well established. The clinical efficacy of ARBs to prevent atrial fibrillation (AF) so far only has been shown in patients with structural heart disease. Here, we report the primary outcome of the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF) trial, which investigated the effect of olmesartan medoxomil compared with placebo on AF burden in patients with paroxysmal AF without structural heart disease. Methods and Results- The ANTIPAF trial was a prospective, randomized, placebo-controlled, multicenter trial analyzing the AF burden (percentage of days with documented episodes of paroxysmal AF) during a 12-month follow-up as the primary study end point. Four hundred thirty patients with documented paroxysmal AF without structural heart disease were randomized to placebo or 40 mg olmesartan per day. Concomitant therapy with ARBs, angiotensin-converting enzyme inhibitors, and antiarrhythmic drugs was prohibited. Patients were followed using daily transtelephonic ECG (tele-ECG) recordings independent of symptoms. The intention-to-treat population of the trial encompassed 425 patients (placebo group, n=211; olmesartan group, n=214). A total of 87 818 tele-ECGs were analyzed in these patients during follow-up (placebo group, 44 888 ECGs; olmesartan group, 42 930 ECGs). Thus, a mean of 207 tele-ECGs were recorded per patient. The primary end point (AF burden) was not different between the 2 groups (P=0.770). Secondary outcome parameters, including quality of life, also were not different. In particular, time to first AF recurrence, time to persistent AF, and number of hospitalizations were not different between the 2 groups. The time to prescription of recovery medication (amiodarone) was the only parameter showing an intergroup difference, with earlier prescription of amiodarone in the placebo group (P=0.022). Conclusions- One year of ARB therapy per se does not reduce the number of AF episodes in patients with documented paroxysmal AF without structural heart disease. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00098137.