Background: MicroRNAs (miRNAs) are endogenous small RNAs that are 21-25 nucleotides in length. Recently, plasma miRNAs have been reported to be sensitive and specific biomarkers of various tissue injuries and pathological conditions. The goal of this study was to assess plasma miRNA profiles and to identify plasma miRNAs that are differentially expressed in patients with heart failure. Methods and Results: A total of 33 patients with ischemic heart diseases and 17 asymptomatic controls were recruited. In 10 patients with heart failure, miRNAs were assessed at both NYHA IV and III. miRNA array analyses were found to be not appropriate for plasma miRNA profiling. The plasma concentrations of well-characterized miRNAs (miR-126, 122 and 499) were assessed by a real-time reverse transcription-polymerase chain reaction using an artificial small RNA as an internal standard. Plasma concentrations of miR-126 were negatively correlated with age and logBNP. In 10 patients with heart failure, plasma concentrations of miR-126 were up-regulated with improvement of the NYHA class from IV to III. Conclusions: The plasma concentration of miR-126 was negatively correlated with age and NYHA class, and could be a useful biomarker for heart failure. (Circ J 2011; 75: 336-340)