Intravenous (i.v.) recombinant tissue plasminogen activator (rtPA) remains the only approved therapy for acute ischemic stroke. However, the use of i.v. thrombolysis is restricted to a minority of patients by the rigid 3-h time window. Modern imaging-based selection algorithms that can identify penumbra have been proposed as methods to extend the window and to select patients more likely to respond favorably or unfavorably to i.v. thrombolysis. We aim to compare the safety and efficacy of multiparametric computed tomography (CT)-based i.v. thrombolysis after 3-9 h of symptom onset with standard CT-based thrombolysis within 3 h and with CT-based thrombolysis or placebo after 3-6 h from the pooled data of the large stroke rtPA trials. The imaging-based thrombolysis trial in acute ischemic stroke-II study is a prospective, multicenter and assessor-blind controlled study. The primary efficacy outcome will be a favorable outcome at 90 days defined as a modified Rankin Scale and reperfusion improvement 24-36 h after treatment; the primary safety end-point outcome will be intracerebral hemorrhage 24-36 h after treatment. We aim to include 200 patients by 2010. It is registered with IRCTN number: ISRCTN12033002.