We sought to assess the anti-inflammatory properties of unfractionated heparin (UFH) in patients with ischemic stroke treated within 24 h from the onset of symptoms. We studied prospectively 167 patients that received 1000 IU/h intravenous UFH (n=70) or 300 mg oral aspirin (n=97) at a mean treatment delay of 6.7 h. Repeated plasma levels of interleukin (IL)-6, IL-10, IL-4, tumor necrosis factor (TNF)-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were compared in both groups using multivariate analyses. Whereas TNF-alpha and sICAM-1 decreased at 48 h, IL-6, IL-4, and sVCAM-1 increased compared with baseline values (P<0.01). The rise of sVCAM-1 levels at 48 h was significantly lower in patients treated with UFH (P=0.017) and a two-fold increase of baseline sVCAM-1 was an independent predictor of poor outcome (odds ratio, 2.19, 1.1-4.39). These results suggest that adjusted high-dose UFH has anti-inflammatory effects which might improve recovery if administered early after stroke onset.