Heat shock protein (HSP) 60 is induced by a variety of stressors, including oxidative stress and inflammation, and it plays a protective role against stress-induced cardiomyocyte injury. Recently, it has been reported that HSP 60 exists in the circulation. Chronic heart failure (CHF) is characterized by systemic abnormalities, and the myocardium is exposed to various stressors. However, the clinical significance of serum HSP 60 has not been examined in CHF. Therefore, the purpose of this study was to examine whether HSP 60 is correlated with the severity of CHF and whether HSP 60 can predict clinical outcomes in patients with CHF. Serum HSP 60 levels were measured in 112 patients with CHF and 62 control subjects. Serum HSP 60 levels were higher in patients with CHF than in control subjects and increased with advancing New York Heart Association functional class. There were 37 cardiac events during a mean follow-up period of 569 +/- 476 days (range 17 to 1,986). Serum HSP 60 levels were higher in patients with cardiac events than in event-free patients. Patients were divided into 4 groups on the basis of HSP 60 level. Cox proportional-hazards regression analysis and Kaplan-Meier analysis revealed that the fourth quartile was associated with the greatest risk for cardiac events. In conclusion, serum HSP 60 level was related to the severity of CHF and associated with a high risk for adverse cardiac events in patients CHF.