Atrial natriuretic peptide (ANP) deficiency is thought to be one of the causes of heart failure induced by atrial fibrillation (AF). Although ANP deficiency is thought to occur as a result of atrial remodeling, data to explain this mechanism are limited. The purpose of this study was to investigate the association between ANP and left atrial remodeling or prognosis of heart failure in patients with AF ablation. In total, 373 consecutive patients who underwent initial ablation for persistent AF [age, 67 ± 10 years; female, 97 (26%)] were retrospectively enrolled. ANP and brain natriuretic peptide (BNP) were measured before the procedure and the ANP/BNP ratio was calculated. Left atrial volume index, left atrial appendage emptying velocity, and left atrial low-voltage areas (LVAs) were used as left atrial-remodeling parameters. The primary outcome of heart failure was defined as the composite of all-cause death or hospitalization due to worsening heart failure. The median ANP level was 116 (71-178) pg/ml and the median ANP/BNP ratio was 0.65 (0.46-1.00). The ANP/BNP ratio decreased with increasing left atrial volume index or LVAs and with decreasing left atrial appendage emptying velocity. During the 5-year follow-up, freedom from the primary outcome was significantly lower in patients with ANP/BNP ratio ≤0.65 than in those with ANP/BNP ratio >0.65 (84.6% versus 95.6%, P < 0.01). Secretion of ANP relative to BNP decreased with progression of left atrial remodeling in patients with AF ablation. Furthermore, prognosis of heart failure was poor in patients with a low ANP/BNP ratio.