D-dimer is a fibrin degradation product, and is implicated in pathologies of cardiovascular system. Thrombosis within the vascular system in relation with inflammation and stasis might be associated with poor prognosis in patients with systolic heart failure (HF). In this study we aimed to investigate for relationship between d-dimer levels and cardiovascular mortality in patients with systolic HF. A total of 174 consecutive patients with hospitalized systolic HF were evaluated. All hospitalized patients were obtained d-dimer levels within the first 24 h following admission after obtaining informed consent. Patients were followed up for cardiovascular mortality and 40 (23%) patients died. d-dimer levels were higher among those who died compared to those who survived (2727 +/- A 2569 (710-4438) versus. 1029 +/- A 1319 (303-1061) ng/ml, P < 0.001). Optimal cut-off level of d-dimer to predict cardiovascular mortality was found to be > 1435 ng/ml. D-dimer levels were negatively correlated with ejection fraction, positively correlated with left atrium size and left ventricular diastolic diameter. D-dimer > 1435 ng/ml, age, diabetes mellitus, presence of atrial fibrillation, and creatinine level were found to have prognostic significance in univariate analyses. In multivariate Cox proportional-hazards model, d-dimer > 1435 ng/ml (HR = 3.250, 95% CI 1.647-6.414, P = 0.001), creatinine level (HR = 1.269, 95% CI 1.008-1.599, P = 0.043), and presence of atrial fibrillation (HR = 2.159, 95% CI 1.047-4.452, P = 0.037) remained associated with an increased risk of death after adjustment for variables found to be statistically significant in univariate analysis and correlated with d-dimer level. In conclusion, d-dimer measurement could help risk stratification in patients with systolic HF.