Background-This study examined the impact of different ablation strategies on atrial fibrillation (AF) recurrence and quality of life in coexistent AF and atrial flutter (AFL). Methods and Results-Three-hundred sixty enrolled patients with documented AF and AFL were blinded and randomized to group 1, AF +/- AFL ablation (n=182), or group 2, AFL ablation only (n=178). AF recurrence was evaluated with event recording and 7-day Holter at 3, 6, 9, and 12-month follow-ups. Quality of life was assessed at baseline and at the 12-month follow-up with 4 questionnaires: the Medical Outcome Study Short Form, the Hospital Anxiety and Depression Score, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. Of the 182 patients in group 1, 58 (age, 63 +/- 8 years; 78% male; left ventricular ejection fraction, 59 +/- 8%) had AF+AFL ablation and 124 (age, 61 +/- 11 years; 72% male; left ventricular ejection fraction, 59 +/- 7%) had AF ablation only. In group 2 (age, 62 +/- 9 years; 76% male; left ventricular ejection fraction, 58 +/- 10%), only AFL was ablated by achieving bidirectional isthmus conduction block. Baseline characteristics were not different across groups. At 21 +/- 9 months of follow-up, 117 in group 1 (64%) and 34 in group 2 (19%) were arrhythmia free (P<0.001). In group 1, scores on most quality-of-life subscales showed significant improvement at follow-up, whereas group 2 patients derived relatively minor benefit. Conclusions-In coexistent AF and AFL, lower recurrence rate and better quality of life are associated with AF ablation only or AF+AFL ablation than with lone AFL ablation. Furthermore, quality of life directly correlates with freedom from arrhythmia, as shown in this study for the first time in patients blinded to the procedure. Clinical Trial Registration-URL: http://www.clinicaltrial.gov/. Unique identifier: NCT01439386. (Circulation. 2013;127:1853-1860.)