AIMS: Here, the aim is to assess long-term clinical variation (CV) of N-terminal pro-brain natriuretic peptide (NT-proBNP) in stable chronic heart failure (CHF) patients. The proposed use of NT-proBNP for monitoring of CHF patients will require accurate information about long-term CV of the peptide. METHODS AND RESULTS: Medication, biochemical variables, and NYHA class were recorded at 1-year and 2-year follow-up in patients treated in our heart failure clinic. Only patients without changes in medication and the NYHA class who were not hospitalized or died in the period from first follow-up to 12 months after the second follow-up were included. A total of 78 patients fulfilled the criteria, and year-to-year CV was calculated to 30% (median) (range: 0-111%) (% changes range: -87 to 397%). Log transformation of NT-proBNP (skewed to the right) reduced the year-to-year CV to 4.7% (range: 0-22%) (% changes range: -18 to 38%). CONCLUSION: Long-term CV of plasma concentrations of NT-proBNP in stable CHF patients is 30%, but the variation is substantial. Therefore, high long-term CV of NT-proBNP does not necessarily carry prognostic significance within the subsequent 12 months. Plasma concentrations of NT-proBNP followed a lognormal distribution, and the low CV of log(NT-proBNP) indicate that NT-proBNP levels are constant during stable conditions.