BACKGROUND Angiotensin-converting enzyme inhibitors (ACEIs) reduce the incidence of atrial fibrillation (AF). OBJECTIVE The purpose of this study was to assess the impact of upstream ACEI therapy on postablation AF recurrence and hospitalization in patients with low left ventricular ejection fraction (LVEF). METHODS Three hundred forty-five consecutive patients undergoing first AF ablation with low LVEF (<= 45%) were classified into group 1 (ACEI+, n = 187 [54%], of whom 44 patients [23.5 /0] had paroxysmal AF [PAF]) or group 2 (ACEI, n = 158 [46 /0]; 31 of these 158 patients [19.6%] had PAF). Additionally, 703 consecutive patients with LVEF >45% undergoing first AF ablation were included for a secondary analysis to evaluate the effect of ACEI treatment in normal ejection fraction. In group 1, ACEI therapy started >= 3 months before ablation and continued through follow-up. RESULTS Baseline characteristics were similar except for hypertension, which was significantly more prevalent in ACEI+ (71 /0 vs 51%, P <.001). At 24 +/- 7 months of follow-up, 109 nonparoxysmal AF patients in group 1 (76%) and 81 (64 /u) in group 2 (P =.015) were recurrence free. In multivariate analysis, ACEI therapy was an independent predictor of recurrence (hazard ratio for ACEI-, 1.7, 95% confidence interval 1.1-2.7; P =.026]. However, among PAF patients, ACEI use was not associated with ablation success (80% vs 77% in ACEI+ and ACEI, respectively; P =.82). In the normal-EF population, the success rates between ACEI+ and ACEI cohorts were similar (71% vs 74%, P =.31). After the index procedure, 17 patients (9.1%) in the ACEI+ group and 28 (17.7%) in the ACEI cohort (P=.02) required rehospitalization, for a 49% relative risk reduction (relative risk 0.51, 95% confidence interval 0.29-0.90). CONCLUSION Preablation use of an ACEI is associated with improvement in ablation outcome in patients with nonparoxysmal AF with low LVEF.