The relationship between natriuretic peptides and atrial distension is not fully understood. We sought to examine their interrelationship and how they relate to atrial fibrillation (AF) recurrence following catheter ablation. We analyzed patients enrolled in the AMIO-CAT trial (amiodarone vs. placebo for reducing AF recurrence). Echocardiography and natriuretic peptides were assessed at baseline. Natriuretic peptides included mid-regional proANP (MR-proANP) and N-terminal proBNP (NT-proBNP). Atrial distension was assessed by left atrial strain measured by echocardiography. The endpoint was AF recurrence within 6 months after a 3-month blanking period. Logistic regression was used to assess the association between log-transformed natriuretic peptides and AF. Multivariable adjustments were made for age, gender, randomization, and left ventricular ejection fraction. Of 99 patients, 44 developed AF recurrence. No differences in natriuretic peptides nor echocardiography were observed between the outcome groups. In unadjusted analyses, neither MR-proANP nor NT-proBNP were significantly associated with AF recurrence [MR-proANP: OR = 1.06 (0.99–1.14), per 10% increase; NT-proBNP: OR = 1.01 (0.98–1.05), per 10% increase]. These findings were consistent after multivariable adjustments. However, atrial strain significantly modified the association between MR-proANP and AF (p for interaction = 0.009) such that MR-proANP was associated with AF in patients with high atrial strain [OR = 1.24 (1.06–1.46), p = 0.008, per 10% increase] but not in patients with low atrial strain. In patients with high atrial strain, an MR-proANP > 116 pmol/L posed a fivefold higher risk of AF recurrence [HR = 5.38 (2.19–13.22)]. Atrial natriuretic peptide predicts AF recurrence in patients with preserved atrial distension. Assessing atrial strain may assist the interpretation of natriuretic peptides. Graphical abstract: [Figure not available: see fulltext.].