Aim:Intraventricular injection of a thrombolytic agent appears to be effective in the lysis of intraventricular hematoma, and improves the final clinical outcome. In this study, we evaluated the effectiveness of intraventricular injection of rt-PA (Actilyse) in patients with spontaneous intraventricular hemorrhage (IVH) who had undergone external ventricular drainage (EVD).Material and Methods:This randomized clinical trial recruited 60 patients with spontaneous IVH who had undergone EVD due to the signs of hydrocephalus. The patients were randomly divided into two groups, including a group receiving intraventricular injection of rt-PA and the other normal saline.Results:Both groups receiving rt-PA Actilyse (n = 28) or placebo (n = 32) were male by majority (58.33%). We found no difference in the prevalence of meningitis and brain infection (35.7% vs. 37.5%, P = 0.665). Changes in hematoma volume at the end of the fourth day compared to the first day after EVD differed significantly between the two groups (P = 0.004). The majority (64.29%) showed a decrease in the rt-PA group, but in the placebo group, the majority (53.13%) remained constant. As a result, changes in the rt-PA group were significantly higher than those in the placebo group. Improvements in the level of consciousness (GCS) at the end of the fourth day compared to the first day after EVD implantation was 1.07 units in the Actilyse group and -1.91 in the placebo group. As shown, the fourth day showed significant differences between the two groups (P<0.001). Improvements in the Glasgow Coma Scale (GCS) were observed at the end of the period. Conclusion:It can be concluded that intraventricular injection of rt-PA (Actilyse) can effectively reduce the volume of hematoma and improve the level of consciousness (GCS) during treatment. Intraventricular injection of 2-mg rt-PA is safe for patients and does not cause any acute complications such as cerebral hematoma expansion.