The efficacy and safety of pentoxifylline were assessed in 297 adult patients with ischemic stroke in a multicenter, double-blind, randomized and placebo-controlled trial. Treatment was started within 12 hours after the stroke onset. Study medication was administered intravenously continuously (16 mg/kg/day, maximum 1,200 mg/day) for 3 days and per os (400 mg t.i.d.) for the remainder of 28 days. Demographic data were comparable, and functional impairment and mortality (pentoxifylline 12%, placebo 10%) were not different between the two groups. Neurologic deficit scores improved from baseline admission scores during the 4-week study in both groups but did not differ between groups at admission or throughout the study except during the first few days when the consciousness level (Days 1 and 2), motor function (Days 1 and 2), cranial nerve function (Days 1-4), and total neurologic deficit scores (Days 1 and 2) were better in the pentoxifylline group than in the placebo group, especially in a subset of patients with severe deficits at admission. Laboratory values and side effects were also comparable between groups. Our study indicates that pentoxifylline can be given safely in patients with acute ischemic stroke. Although pharmacologic effects were present during the first few days, the clinical benefits were small and not sustained.