Heart failure is associated with low-grade inflammation. In the present study we sought to assess the prognostic impact of orosomucoid, a marker of inflammation, in outpatients with heart failure. In outpatients with chronic heart failure (no change in clinical status and/or therapy >3 months prior to inclusion), baseline levels of orosomucoid were determined. Clinical follow-up was obtained and the rate of heart failure-related deaths and hospitalisations recorded. A total of 134 patients (median age 71, 33.3 % female, mean left ventricular ejection fraction [LVEF] 36 %) were included. During a median follow-up of 695 (456–811) days, 54 patients (40.1 %) experienced an event. On Cox multivariate analysis, orosomucoid levels above the median (>497 mg/l) emerged as an independent predictor of prognosis (hazard ratio = 2.86, 95 % confidence interval 1.48–5.52 after adjusting for age, gender, ischaemic vs. non-ischaemic aetiology, LVEF, NT-proBNP and NYHA class). Orosomucoid levels are an independent predictor of heart failure-related mortality and hospitalisations in patients with chronic heart failure.