PURPOSE Atrial fibrillation (AF) is the most common arrhythmia and has an increasing impact on public health because of its morbidity and mortality. Clinical and diagnostic tests to predict the recurrence of arrhythmia and clinical events before AF becomes permanent are still an open issue. METHODS 307 out of 1442 patients in sinus rhythm, at high risk of recurrence of AF enrolled in the GISSI-AF study, participated in a substudy with echocardiographic and biohumoral evaluation at baseline and at 12-month follow-up. The relations between biomarker concentrations and echocardiographic parameters with study endpoints in 1 year, were analysed by a stepwise multivariable Cox model (entry criteria p < 0.5 and stay criteria p < 0.2). RESULTS The echocardiographic variables, cardiac markers and clinical variables considered in the statistical model indicated a higher concentration of NT-proBNP at baseline as the strongest factor related to time of first AF recurrence (HR 1.42; 95 %CI 1.23-1.46), first CV hospitalization (HR 1.58; 95 %CI 1.31-1.92) and increasing duration of recurrent AF (OR 2.16; 95 %CI 1.52-3.08). Valsartan treatment was not related to clinical events. CONCLUSIONS In patients in sinus rhythm with a history of AF a higher concentration of NT-proBNP at baseline was the strongest independent risk factor for first AF recurrence and its duration, and for the first hospital admission for cardiovascular reasons.