Objective: Traumatic intracranial epidural hematoma is considered to be the serious complication of head injury requiring appropriate evaluation and surgical intervention. Although craniotomy provides an effective evacuation of the hematoma, there is an insufficient data to support one particular surgical treatment method. The objective of this study is to address the effectiveness of Urokinase instillation via single burr hole in different time interval. Method: Forty two patients with traumatic epidural hematoma, ranging between 15 and 71 years who meet the inclusion criteria were selected for the retrospective study. All the patients were surgically treated in the First Affiliated Hospital of Liaoning Medical University from January 2013 to June 2015. Result: The common complication encountered in this study was headache, dizziness, fever and re-bleeding. In Group-A, 4 (19%) patients complained of headache, 5 (23.8%) dizziness, 1 (4.7%) fever and re-bleeding occurred in 2 (9.5%) patients. In Group-B, 2 (9.5%) patients complained of headache, 1 (4.7%) dizziness, 1 (4.7%) fever and 1 (4.7%) re-bleeding. Out of forty two patients, 3 (7.1%) patients encountered re-bleeding and received craniotomy. In this study, Group B demonstrates better outcome than Group A (P < 0.028). Conclusion: Single burr hole with Urokinase instillation is safe, feasible and effective technique in the treatment of traumatic epidural hematoma in selected cases where close regular clinical and radiological monitoring is possible.