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Importance: Catheter ablation is effective in reducing atrial fibrillation (AF), but the association of ablation for AF with quality of life is unclear., Objective: To evaluate whether the procedural outcome of ablation for AF is associated with quality of life (QOL) measures., Design, Setting, and Participants: This was a prespecified secondary analysis of the Substrate and Trigger Ablation for Reduction of Atrial Fibrillation-Part II (STAR AF II) prospective randomized clinical trial, which compared 3 strategies for ablation of persistent AF. This analysis included 549 of the 589 patients enrolled in the trial who underwent ablation. Enrollment occurred at 35 centers in Europe, Canada, Australia, China, and Korea from November 2010 to July 2012. Data for the current study were analyzed on December 11, 2019., Interventions: Patients underwent AF ablation with 1 of 3 ablation strategies: (1) pulmonary vein isolation (PVI), (2) PVI plus complex fractionated electrograms, or (3) PVI plus linear lesions., Main Outcomes and Measures: Quality of life was assessed at baseline and at 6, 12, and 18 months after ablation for AF using the 36-Item Short Form Health Survey and the EuroQol Health-Related Quality of Life 5-Dimension 3-Level questionnaire. Scores were also converted to a physical health component score (PCS) and a mental health component score (MCS). Individual AF burden was calculated by the total time with AF from Holter monitors and the percentage of transtelephonic monitor recordings showing AF., Results: Among the 549 patients included in this secondary analysis, QOL was assessed in 466 (85%) at baseline and at 6, 12, and 18 months after ablation for AF. The mean (SD) age of the study population was 60 (9) years; 434 (79%) individuals were men, and 417 (76%) had continuous AF for 6 months or more before ablation. The AF burden significantly decreased from a mean (SD) of 82% (36%) before ablation to 6.6% (23%) after ablation (P < .001). Significant improvements in mean (SD) PCS (68.3 [20.7] to 82.5 [18.6]) and MCS (35.3 [8.6] to 37.5 [7.6]) occurred 18 months after ablation (P < .05 for both). Significant QOL improvement occurred in all 3 study arms and regardless of AF recurrence, defined as AF episodes lasting more than 30 seconds: for no recurrence, mean (SD) PCS increased from 66.5 (20.9) to 79.1 (19.4) and MCS from 35.3 (8.7) to 37.7 (7.7); for recurrence, mean (SD) PCS increased from 70.2 (20.4) to 86.4 (16.8) and MCS from 35.3 (8.6) to 37.1 (7.4) (P < .05 for all). When outcome was defined by AF burden reduction, in patients with less than 70% reduction in AF burden, the increase in PCS was significantly less than in those with greater than 70% reduction, and only 3 of 8 subscales showed significant improvement., Conclusions and Relevance: In this secondary analysis, decreases in AF burden after ablation for AF were significantly associated with improvements in QOL. Quality of life changes were significantly associated with the percentage of AF burden reduction after ablation., Trial Registration: ClinicalTrials.gov Identifier: NCT01203748.