Abstract Background Catheter ablation (CA) is a well-established treatment option for recurrent atrial fibrillation (AF), and has shown to outperform antiarrhythmic drugs in prevention of AF recurrences in numerous studies. However, up to 50% of patients with persistent AF (peAF) will experience recurrences after first-time CA. Improving treatment for these patients involves, choosing the right patients for the ablation procedure, optimizing the timing of the procedure, and using the most effective ablation strategy. This will benefit not only the patients, but also target recourse use in the healthcare system. Purpose To identify characteristics and comorbidities of patients with peAF associated with a reduced risk of recurrence after CA. Additionally, to investigate the optimal timing and ablation strategy. Methods This observational cohort study was conducted using real-life data from the Danish healthcare registries. All patients with peAF, >18 years of age, who were assigned to first-time AF ablation, were included within the study period from January 1st 2010 to December 31st 2018. A composite endpoint for AF recurrences was defined as either AF admission, electric cardioversion, use of antiarrhythmic drugs or re-ablation after a 3-month blanking period. We followed the patients in the registries for up to 5 years. A Cox proportional hazards analysis was performed to identify specific patient characteristics, comorbidities, timing of ablation and ablation strategy associated with reduced risk of AF recurrences after ablation. Results The study cohort consisted of 2,123 patients with peAF undergoing first-time CA. Median age was 63 years [IQR: 56.10;68.90], 77.7% were male, and mean BMI was 28.40 (SD: 4.97). Mean diagnosis-to-ablation-time (DAT) was 3.56 years (SD: 4.25) and mean follow-up time was 928.3 days (SD: 829.62). Most prevalent co-morbidities were hypertension (59.1%), ischemic heart disease (16.9%), and heart failure (HF) (27.7%) (Table 1). Patients characterized by male sex (HR: 0.80, 95% CI 0.69-0.93), age 60-70 (HR: 0.79, 95% CI 0.67-0.93), and absence of co-morbidities such as HF (HR: 0.81, 95% CI 0.70-0.94) and chronic obstructive pulmonary disease (COPD) (HR: 0.58, 95% CI 0.44-0-75), were observed with a significantly reduced relative risk of recurrent AF. Short DAT(<1 year) was associated with a 24% lower risk of recurrence compared to longer (>2 years). Furthermore, PVI Plus (additional ablation to PVI) was not significantly associated with a reduced risk of recurrences (HR: 1.10, 95% CI 0,92-1.31) (Figure 1). Conclusion To obtain rhythm control for patients with peAF is a great challenge. This observational study with more than 2,000 patients, identifies patients most likely to benefit from CA. Lower recurrence rates were observed in younger patients (<70 years), absence of especially HF and COPD, and early ablation (<1 year). Notably, PVI plus did not reduce the risk of recurrences.