The purpose of this study was to assess the feasibility and long-term results of empirical isolation of both superior pulmonary veins in patients with chronic AF. Although localizing and ablating the focal triggers of AF has been proven an effective approach, this strategy is time consuming, often requires multiple procedures, and carries the risk of pulmonary vein stenosis. Whether ostial electrical isolation of the superior pulmonary veins, without initial detailed mapping, is a more efficient approach is not known. The study included 71 consecutive patients who had chronic AF. Using a nonfluoroscopic electroanatomic mapping system, the left and right superior pulmonary veins were ablated circumferentially at the venoatrial junction, with the aim of achieving electrical isolation of the veins. Following ablation, if frequent atrial ectopies were present, mapping and ablation were considered. The patients were periodically followed with 48-hour Holter and loop recorder monitoring. After the ablation of the right and left superior pulmonary veins 59 (83%) of 71 patients maintained sinus rhythm without premature atrial beats. The remaining 12 patients underwent further mapping and ablation including 5 patients who required isolation of the left inferior pulmonary veins. True electrical isolation could be achieved only in 45 (31%) of the 147 targeted veins. At the latest follow-up (mean 29 +/- 8 months), 80% of the patients with upper vein isolation remained in sinus rhythm off medications, 62% of the patients maintained sinus rhythm on previously ineffective medications, and 17% continued to be in AF. Fourteen (20%) patients developed intermittent episodes of left atrial flutter, and mapping in these patients revealed large electrically silent areas in the left atrium. Empirical isolation of pulmonary veins appeared to be an effective approach to help maintain sinus rhythm in patients with chronic AF. True electrical isolation of the pulmonary veins was associated with a higher likelihood of long-term success. Left atrial flutter was seen in a significant number of patients at long-term follow-up.