Aims: Catheter ablation (CA) is recommended for patients with atrial fibrillation (AF) after failure of antiarrhythmic drugs (AADs). The role of CA as 'initial therapy' for AF is to be determined. Methods and results: Following PRISMA guideline an up-to-date pooled analysis of randomized data comparing ablation vs. AADs as first-line therapy for symptomatic AF was performed. The primary outcome was recurrence of atrial tachyarrhythmia. The secondary outcomes were improvement in quality-of-life (QoL) and major adverse events. A total of 997 patients from five randomized trials were enrolled (mean age 57.4 years, 68.6% male patients, 98% paroxysmal AF, mean follow-up 1.4 years). The baseline characteristics were similar between the ablation and AADs group. Overall pooled analysis showed that, as compared with AADs, CA as first-line therapy was associated with significantly higher freedom from arrhythmia recurrence (69% vs. 48%, odds ratio: 0.36, 95% confidence interval: 0.27-0.48, P < 0.001). This significance was maintained in subgroup analyses of 1- A nd 2-year follow-up (P < 0.001). Catheter ablation was associated with significantly greater improvement in QoL regarding AFEQT score and 36-Item Short-Form Health Survey score. The incidence of serious adverse events between ablation and AADs group (5.6% vs. 4.9%, P = 0.62) was similar. Conclusions: Catheter ablation as 'initial therapy' was superior to AADs in maintenance of sinus rhythm and improving QoL for patients with symptomatic paroxysmal AF, without increasing risk of serious adverse events.