||This report evaluates the current state of evidence regarding effectiveness and harms of catheter ablation for atrial fibrillation (AF) with a focus on longer-term outcomes and evidence relevant to the Medicare population. Systematic searches of the following databases: Ovid MEDLINE(R) (from 2005 to November 2014), Cochrane Central (November 2014), and Cochrane Database of Systematic Reviews (from 2005 to November 2014). Using predefined criteria, randomized trials and observational studies comparing the efficacy, effectiveness, or safety of catheter ablation (radiofrequency or cryoballoon ablation) to medical therapy in patients with AF were included. Analyses were stratified by type of AF and length of followup (>12 months vs. </=12 months). The quality of included studies was assessed, data were extracted, results were summarized qualitatively and using meta-analysis, and the strength of the evidence was graded for each primary outcome. Of 3,471 citations identified, 46 studies were included. In the Medicare population, evidence was insufficient for all outcomes. Regarding the longer-term effect of radiofrequency ablation (RFA) versus medical therapy in the general population, low-strength of evidence suggested no statistical differences between groups in all-cause mortality for people with paroxysmal AF. Long-term (>12 months) freedom from any atrial arrhythmia recurrence was greater following RFA versus medical therapy (pooled relative risk [RR] 1.24, 95% confidence interval [CI] 1.11 to 1.47) in paroxysmal AF patients (moderate-strength evidence). There was insufficient evidence to draw conclusions for all other long-term primary outcomes including stroke, myocardial infarction, and congestive heart failure. Regarding the short-term (</=12 months) effect of RFA compared with medical therapy, low strength of evidence suggested no significant differences between groups for all-cause mortality regardless of AF type and myocardial infarction in paroxysmal AF patients. Freedom from short-term recurrence was greater following RFA based on moderate strength of evidence (pooled RR 2.62, 95% CI 1.90 to 3.90). Reablation ranged from 0 to 53.8 percent across AF types and time frames. At 6 months, RFA was associated with better health-related quality of life in those with persistent AF and heart failure (low strength of evidence); however, results were inconsistent across measures and heterogeneity precluded pooling of data or drawing firm conclusions. In terms of harms, no statistical differences in 30-day mortality or stroke or 3-month AF recurrence between groups were found, with low strength of evidence. The pooled risk of cardiac tamponade following RFA was 1.7 percent (95% CI 0.8 to 3.6) for people with paroxysmal AF based on low strength evidence, while evidence was insufficient to draw conclusions regarding persistent AF patients. There was insufficient evidence to draw conclusions regarding efficacy or safety for cryoballoon ablation, with the exception of low strength of evidence for greater freedom from protocol-defined failure (which included freedom from AF) following cryoballoon ablation versus medical therapy. There was insufficient evidence to draw conclusions regarding efficacy or safety for cryoballoon ablation versus RFA or medical therapy. There was insufficient evidence to draw conclusions regarding the efficacy, effectiveness, and safety of catheter ablation in the Medicare population. In the general population, there was moderate evidence that RFA is superior to medical therapy for enhancing patient freedom from recurrence of atrial arrhythmias in both the short and long term regardless of AF type, but reablation was common. RFA does not appear to impact all-cause mortality in the short or long term in those with paroxysmal AF (low strength of evidence); however, there was insufficient evidence to draw conclusions regarding other primary clinical outcomes in the short or long term. Firm conclusions regarding health-related quality of life were not possible given heterogeneity across studies for instruments employed, measurement timing, and clinical characteristics. For harms, no differences between RFA and medical therapy in 30-day mortality, stroke, or 3-month risk of AF were seen, with low strength of evidence. Evidence comparing cryoballoon ablation with medical therapy or with RFA was insufficient to draw conclusions regarding efficacy or safety, with the exception of low strength of evidence for greater freedom from protocol-defined failure following cryoballoon ablation versus medical therapy. To better understand the impact of catheter ablation on key outcomes (stroke, mortality, health-related quality of life, and symptom improvement) compared to other treatment strategies, large methodologically sound studies are needed, particularly on persistent AF patients. Studies with sufficient sample sizes are needed to effectively determine whether catheter ablation versus other treatments will benefit certain patient subgroups more than others, and whether there are subgroups in which catheter ablation might best used as a first- versus second-line treatment.