Introduction: An additional approach may be essential to reduce recurrences of atrial fibrillation (AF) after pulmonary vein isolation (PVI). We examined the efficacy of renin-angiotensin system blockers (RAS-B) in suppressing AF recurrences after PVI. Methods and Results: We retrospectively studied 264 consecutive patients (195 male, median age: 63 years) who underwent successful PVI of paroxysmal (n = 94) or persistent AF (n = 170). RAS-B treatment was performed in 145 patients (angiotensin-converting enzyme inhibitors; n = 13, angiotensin receptor blockers; n = 129, both; n = 3). Echocardiography was performed before and 3 months after the ablation to examine the occurrence of left atrial structural reverse remodeling (LA-RR). After a median follow-up of 195 (interquartile range: 95-316) days, AF recurred in 51 (19.3%) patients. A Cox regression analysis revealed that AF recurrence was significantly lower in the patients with RAS-B than in those without (hazard ratio [HR] = 0.41 [95% confidence interval (CI): 0.23-0.71], P = 0.002). After a multivariate adjustment for potential confounders, the use of RAS-B (HR = 0.39 [95% CI: 0.19-0.77], P = 0.007) and type of AF (HR = 0.30 [95% CI: 0.13-0.66], P = 0.003) were the independent predictors for AF recurrence during the entire follow-up. Although effect of RAS-B was not significant during the early follow-up (<3 month), it was the only independent predictor during the late follow-up (>3 months) (HR = 0.21 [95% CI: 0.08-0.53], P = 0.001). There were no significant differences in LA-RR occurrence regarding RAS-B medication. The use of RAS-B was an independent predictor of late AF recurrences irrespective of an early LA-RR occurrence. Conclusions: Treatment with RAS-B significantly reduced the AF recurrence after PVI. This benefit became more prominent 3 months after the PVI. (PACE 2011; 34:296-303) © 2010 Wiley Periodicals, Inc.