In a prospective observational study, we assessed the relative value of conventional stroke risk factors and emerging markers in the prediction of functional outcome of patients surviving the acute phase of an ischemic non-embolic stroke. All available eligible patients consecutively admitted due to a first-ever acute ischemic non-embolic stroke during a 2-year period were evaluated. In a total of 105 patients (54 males, 51 diabetic) a series of clinical, biochemical and imaging characteristics were recorded, including demographic data, blood pressure, serum glucose, insulin, lipids, inflammatory markers, intima-media thickness of the carotid arteries (IMT), brain damage location and size of the infarct volume. Barthel Activities of Daily Living Index (BI) scale was used to assess the severity of neurological deficit on admission and the functional outcome 6 months after discharge. Brain infarct volume, stroke location in the anterior circulation, age, diabetes mellitus, IMT and plasma interleukin-1beta levels proved to be significant determinants of long-term functional outcome, assessed by BI disability score. ROC curve analyses indicated that the infarct volume is superior to other predictors in the diagnosis of patients with unfavorable functional outcome (BI<95) at 6 months post-discharge (area under the curve, AUC=0.80, 95% confidence interval 0.64-0.95; p=0.003). Significant differences in the mean infarct volume were noted among age tertiles, with the diabetic patients in the 3rd tertile of age experiencing the worst outcome (LSD test, p=0.019). Taken together, the assessment of infarct volume seems to have a significant predictive value regarding long-term functional outcome, especially in the elderly diabetic patients.