The level of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a strong predictor of mortality in patients with acute coronary syndrome and may be a strong prognostic marker in patients with chronic coronary artery disease. We investigated whether NT-pro-BNP could predict in-stent restenosis (ISR) in asymptomatic patients with preserved left ventricular (LV) systolic function who underwent percutaneous coronary intervention. We measured serum NT-pro-BNP levels in 249 patients (61 +/- 9 years of age; 73% men) with preserved LV systolic function (ejection fraction >50%) who underwent follow-up coronary angiography. Initial diagnoses were stable angina in 50 (20%), unstable angina in 133 (53%), and myocardial infarction in 66 (27%). Baseline characteristics between groups with ISR (n = 92) and without ISR (n = 157) were similar. The level of NT-pro-BNP was higher in patients with ISR than in those without ISR (222 +/- 327 vs 94 +/- 136 pg/ml, p = 0.001). In the ISR group, NT-pro-BNP level was higher in patients with left anterior descending coronary artery ISR (n = 53, 312 +/- 479 pg/ml) than in those with left circumflex coronary artery ISR (n = 19, 115 +/- 98 pg/ml, p = 0.018). At the standard cutoff of >200 pg/ml, a high NT-pro-BNP level indicated a high probability of ISR (odds ratio 2.18, 95% confidence interval 1.0 to 4.5, p = 0.038). In multivariate analysis, NT-pro-BNP level was an independent predictor for ISR. In conclusion, NT-pro-BNP could be a predictor of ISR in asymptomatic patients with preserved LV systolic function.