BACKGROUND: With electrogram-guided radiofrequency ablation (RFA) of long-lasting persistent atrial fibrillation (AF), the best results have been reported when complex fractionated electrograms (CFAEs) in both the left (LA) and right (RA) atria were targeted. However, many studies have reported excellent outcomes from RFA of long-lasting persistent AF with the use of other ablation strategies that were limited to the LA. The incremental value of RFA of RA CFAEs is yet to be defined. METHODS AND RESULTS: In 85 patients with long-lasting persistent AF (age=59+/-10 years), RFA was directed at CFAEs in the LA and coronary sinus until AF terminated (19) or all identified LA CFAEs were eliminated. Sixty-six patients who remained in AF were randomly assigned to cardioversion and no further RFA (n=33) or to RFA of RA CFAEs (n=33). RA sites consisted of the crista terminalis (69%), septum (38%), superior vena cava (28%), coronary sinus ostium (22%), and the base of the appendage (31%). AF terminated in 1 (3%) of 33 patients during RA RFA. At 17+/-6 months after a single ablation procedure, 74% of the patients in whom AF terminated during LA RFA were in sinus rhythm. Rates of freedom from AF were similar in the patients randomized to no RFA in the RA (24%) and those randomized to RFA of RA CFAEs (30%, P=0.8). The ablation procedure was repeated in 26 patients (31%) for AF (n=22) or atrial flutter (n=4). At 16+/-7 months after the final procedure, 89% of the patients in whom AF terminated during LA RFA were in sinus rhythm. Among the randomized patients, the proportion of patients who remained in sinus rhythm was similar in patients who did not undergo RFA of RA CFAEs (52%) and those who did (58%, P=0.6). CONCLUSIONS: After RFA of CFAEs in the LA and coronary sinus, ablation of CFAEs in the RA provides little or no increment in efficacy among patients with long-lasting persistent AF.