Background and Purpose-We sought to investigate the feasibility of the combined use of low-dose recombinant tissue plasminogen activator (rtPA) and tirofiban, a glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist, for systemic thrombolysis in acute stroke. Methods-Consecutive patients who were treated with systemic application of low-dose rtPA and body weight-adjusted tirofiban (rtPAϩT group; nϭ37) were evaluated retrospectively during 1999 -2001. Patients in the rtPAϩT group were compared with a group of patients treated with a dose of 0.9 mg/kg body weight in a different center (rtPA group; nϭ119). The 41 patients with infarctions of the middle cerebral artery territory who were not eligible for thrombolytic treatment because of medical contraindications or arrival in the hospital Ͼ3 hours after stroke onset served as controls. For matched comparisons, the National Institutes of Health Stroke Scale on admission and the Rankin Scale on discharge 5 days after stroke were used. Results-The patients treated with rtPAϩT or rtPA improved (PϽ0.05) compared with the controls at discharge; patients in the rtPAϩT and rtPA groups reached a Rankin Scale score of 0 to 2 in 63% and 55%, respectively, while only 16% of the controls achieved this score. Death rates (8% in rtPAϩT group and 5% in rtPA group) were similar among the 2 treatment groups. They included 1 fatal hemorrhage in the rtPAϩT group and 4 fatal hemorrhages in the rtPA group. Five percent of the untreated patients developed symptomatic, nonfatal cerebral hemorrhage. Conclusions-Systemic combined thrombolysis with rtPAϩT seems to be a feasible treatment in acute stroke.