Objective To observe the efficacy and safety of recombinant tissue type plasminogen activa-tor (rt-PA)for the treatment of the patients with wake-up ischemic stroke (WUS)under the guidance of multimode CT. Methods Eighteen patients with WUS (a thrombolytic group)suitable for intravenous thrombolysis after multimode CT imaging screen at the Department of Neurology,Shiyan Hospital of Integrated Traditional and Western Medicine,Hubei Province from October 2012 to October 2014 were enrolled retrospectively. Twenty patients with WUS (a control group)who underwent multimode CT imaging screen were suitable for intravenous thrombolysis,but because of exceeding time window or rejecting thrombolysis and other reasons without having intravenous thrombolysis from February 2012 to February 2014 were enrolled retrospectively. The control group was treated with conventional therapy and the thrombolytic group was treated with rt-PA (0. 9 mg/kg)intravenous thrombolytic therapy. The indicators including fibrinogen (Fib),coagulation function (prothrombin time [PT ]),activated partial thromboplastin time (APTT ), platelet (PLT ),high-sensitivity C-reactive protein (hs-CRP ),National Institute of Health Stroke Scale (NIHSS )scores,and activities of daily living scores (Barthel index)at before treatment and 24 h,7 and 14 days after treatment were observed respectively. The adverse events and complications were documented and compared with the control group. Results There were no significant differences in Fib,PT,APTT, PLT,hs-CRP,NIHSS score and Barthel index before treatment between the thrombolytic group and the con-trol group (all P>0. 05);at day 7 and 14 after treatment in the thrombolytic group,compared with before treatment,Fib (14 d after treatment),PLT,and hs-CRP were decreased,PT and APTT were prolonged,the NIHSS scores were decreased,and Barthel indexes were increased. There were significant differences (all P<0. 05). At day 14 after treatment,there were significant differences in Fib,PT,APTT,hs-CRP,NIHSS scores,and Barthel indexes (Fib:3. 25 ± 0. 38 g/L vs. 3. 55 ± 0. 28 g/L;PT:15. 7 ± 3. 2 s vs. 12. 9 ± 2. 5 s;APTT:42. 7 ± 3. 5 s vs. 38. 7 ± 2. 6 s;PLT:[189 ± 26]× 109/L vs. [201 ± 23]× 109/L;hs-CRP:5. 7 ± 0. 6 mg/L vs. 11. 3 ± 2. 2 mg/L;NIHSS scores:5. 6 ± 2. 4 vs. 9. 2 ± 4. 5;and Barthel indexes:68 ± 15 vs. 47 ± 5)between the two groups (all P <0. 05). Except 1 patient occurred symptomatic intracerebral hemorrhage after thrombolysis,no other serious complications were observed in the thrombolytic group. One patient in the control group had stress gastric ulcer and bleeding,no symptomatic intracerebral hemorrhage occurred. Conclusion Multimode CT guidance can be used as a reliable imaging evidence for patients with WUS expanding intravenous thrombolytic time window. Under the multimode CT guidance, using rt-PA for intravenous thrombolytic therapy has a certain efficacy.