OBJECTIVES: There is increasing evidence that inflammation and hypercoagulability play an important role in the pathophysiology of acute ischaemic stroke. We examined the in-hospital prognostic value on mortality of C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), fibrinogen and D-dimer in middle-aged ischaemic stroke patients. MATERIALS AND METHODS: We recruited 231 consecutive patients <66 years with acute ischaemic stroke. CRP, TNF-alpha, fibrinogen and D-dimer levels were determined within 12 h from admission. RESULTS: Fifteen (6.5%) patients died during hospitalization. CRP, fibrinogen and D-dimer levels were significantly higher in patients who died compared with those who survived but only CRP and fibrinogen were independently associated with death, after adjusting for various confounding factors. For 1 mg/l increase in CRP there was a 20% higher risk of dying while for 10 mg/dl increase in fibrinogen the additive risk was 18%. CRP levels >18 mg/l and fibrinogen levels >490 mg/dl were the optimal points that discriminated those who died from the rest. CONCLUSIONS: CRP and fibrinogen levels can predict independently the risk of early death in middle-aged ischaemic stroke patients emphasizing the role of inflammation and coagulation in the evolution of ischaemic stroke.