We aimed to estimate the prevalence of elevated D-dimer levels in all chronic hemodialysis patients and those without additional disease, and to identify factors associated with increased D-dimer. In 167 chronic hemodialysis patients from our center, D-dimer was measured before dialysis. The effects of age, C-reactive protein (CRP), recent acute illness, vascular access, anticoagulation type, dialysis vintage, and chronic diseases, considered to predispose for increased D-dimer levels, were analyzed. The median D-dimer in the whole group was 966 (inter-quartile range [IQR] 524-1947) μg/L and was positive (>500 μg/L) in 75% of cases. D-dimer was positive in 91% of patients with acute illness, 76% of those with predisposing chronic diseases, but was still positive in 52% of patients without additional disease (i.e., acute illness or predisposing chronic diseases) - median D-dimer was 538.5 (IQR 359-966) μg/L. D-dimer was correlated to patients' age, but not dialysis vintage. In univariate analysis, the D-dimer levels were significantly higher in patients with atrial fibrillation, ischemic heart disease, recent acute illness, increased CRP, dialyzed over a catheter, and on citrate anticoagulation. Multivariate logistic regression showed that only age >65 years (odds ratio [OR] 2.93), catheter (OR 4.86), and positive CRP (OR 4.07) were independently associated with positive D-dimer at 500 μg/L cut-off, while the significance of age disappeared at 2000 μg/L cut-off. To conclude, the high prevalence of positive D-dimer values even in hemodialysis patients without additional disease limits the use of D-dimer for exclusion of thromboembolic diseases in hemodialysis patients.