Abstract Background AF is reported in up to 20% of patients with Chagas, a prevalent disease in Latin-America. PV isolation (PVI) in the cornerstone of AF ablation. However, in Chagas cardiopathy (ChC), microvascular and autonomic abnormalities, atrial fibrosis and sinoatrial dysfunction are possible mechanisms of AF. Therefore, the results of PVI may be different in this subgroup. Objectives To describe long-term results of AF ablation in pts with Chagas versus non-Chagas disease (ChC x NonCh) and evaluate risk factors for post-ablation recurrence. Methods This is a prospective, single-center study that included pts with nonvalvular AF who underwent PVI between 2013 and 2016. All procedures were guided by eletroanatomic mapping and intracardiac echocardiogram. Categorical variables were analyzed using chi-square test and numerical variables with t-student test. Binary logistic regression was performed to identify independent predictors of recurrence of any sustained atrial tachyarrhythmias. Results Ablation was performed in 160 pts (54±15 yo, 59% male): 42 pts with ChC (26%, 62±8 yo) and 118 NonChC (74%, 53±15 yo; p<0,001)). There was no difference in AF type (38x34% paroxysmal, 42x43% persistent, and 19x23% long-term persistent, p=NS) and left atrium diameter (38±5 vs 40±8mm, p=NS). In ChC the mean CHADSVASC score was higher (2.4 vs 1.4, p<0,001) and LVEF was lower (52±18% vs 64±8%, p=0.02). After a follow-up of 31±14 mo and 1.1 ablation per group, recurrence of AF/AT was higher in ChC (33% vs 14%, p=0.03) although more pts with Chagas were on AAD (71 vs 31%, p<0,001). During follow-up, occurrence of embolic events and cardiac or all-cause mortality were not different between groups (0% vs 1.7%, p=NS and 2.4 vs 1.7% p=NS; for ChC vs and NonChC, respectively). At multivariate analysis, long-term persistent AF, hypertension and Chagas disease (HR= 2.21, 3.36 and 3.16, respectively) were independent predictors of recurrence. Conclusions Chagas disease is an independent predictor of recurrence after PVI. Further studies should address which strategy is more appropriate to this group of patients.