Objective:To evaluate the clinical efficacy and safety of neuro-endoscopic evacuation and microsurgery via keyhole approach in early spontaneous supertentorial intracerebral hemorrhage (ICH). Methods:A prospective multi-center randomized controlled trial was performed; 114 patients with spontaneous supertentorial ICH (time from onset to surgery<6 h) admitted to Departments of Neurosurgery, Shunde Hospital of Southern Medical University, Jiangmen Central Hospital, Affiliated Hospital of School of Medicine of Yanbian University from January 2019 to December 2021 and met the surgical indications were selected. They were divided into endoscopic group (evacuation of intracerebral hematoma under neuroendoscope, n=71) and microscopic group (microsurgery of intracerebral hematoma via keyhole approach, n=43) according to different surgical methods. After 1:1 propensity score matching of the general data, surgical time, hematoma clearance rate, early postoperative re-bleeding rate, Glasgow coma scale (GCS) scores 7 d after surgery, activity of daily living (ADL) scores 6 months after surgery, mortality, and surgery-related complications of 66 patients (33 from each group after matching) were compared. Results:The difference of surgical time between endoscopic group and microscopic group was statistically significant (125[102, 157] mins vs. 175[125, 260] mins, P<0.05). However, hematoma clearance rate (93.00%[80.88%, 96.52%] vs. 93.31%[88.15%, 96.03%]), early postoperative re-bleeding rate (15.2% vs. 9.1%), GCS scores 7 d after surgery (13[10, 15] vs. 12[8, 14]), ADL scores 6 months after surgery (65[45, 85] vs. 55[0, 85]), mortality rate (18.2% vs. 21.2%) and incidences of postoperative intracranial infection and acquired pulmonary infection were not statistically significant between the two groups ( P>0.05). Conclusion:Comparing with microsurgery via keyhole approach, neuro-endoscopy could shorten the surgical time, but not improve the prognosis or safety in early spontaneous supertentorial ICH patients.