Background Heat shock proteins (HSPs) represent intracellular mechanisms of stress response. Clinical implications of their (systemic) expression in patients with chronic heart failure (HF) remain inconclusive. Methods In outpatients with chronic stable HF plasma HSP27 levels were measured using ELISA. Patients were followed for a minimum of one year, and a multivariate Cox proportional hazard model was built for cardiovascular death or HF-associated hospitalisations. Results A total of 134 patients with chronic HF (mean age 71 ± 10 years, 34% female, mean LVEF 36 ± 12%) were included. During a mean follow-up of 527 ± 260 days, 44 patients (33%) experienced an event. Mean time to event was 350 ± 236 days. In a Kaplan-Meier survival analysis HSP27 levels above the median (3820 pg/ml) indicate a higher risk for an event (p = 0.03). Increased HSP27 levels remained an independent predictor of events (HR, 2.33 CI 95% 1.12–4.87, p = 0.024) even after adjustment for age, gender, NT-proBNP, LVEF, aetiology, smoking status, kidney function and NYHA class. Conclusions HSP27 is an independent predictor of prognosis in chronic HF. Our findings suggest that HSP27 may improve risk-stratification in chronic HF beyond known prognostic predictors. [ABSTRACT FROM AUTHOR]