Studies on the use of therapeutic hypothermia (TH) to improve the outcome of high-grade aneurysmal subarachnoid hemorrhage (aSAH), show promising, though conflicting results because of the lack of high-quality trials. The aim of this study is to evaluate the safety and efficacy of TH (maintaining bladder temperature at 33 °C for ≥72 h) to treat patients with high-grade aSAH (Hunt-Hess grade IV-V). A multicenter, randomized, controlled clinical trial will be conducted for October 2020 to September 2024 involving 10 clinics. Patients who meet the inclusion criteria will be randomized 1:1 to a TH group and a normothermia group. The trial will enroll 96 participants in TH group and normothermia one, respectively. The trial was registered with ClinicalTrials.gov (NCT03442608) on February 22, 2018. Following conventional treatment for aSAH, patients will undergo either TH for at least 72 h or normothermia. The primary endpoint is the Glasgow outcome scale at 6 months after bleeding. The secondary endpoints are: (I) mortality at 6 months after bleeding; (II) intracranial pressure; (III) intensive care unit stay; and (IV) hospital stay. The safety endpoints include neurological, infectious, intestinal, circulatory, coagulation, and bleeding complications, electrolyte disorders, and other complications. If the study hypothesis is confirmed, TH at 33 °C in patients with high-grade aSAH may become a promising treatment strategy for improving 6-month outcome. The trial has been registered at ClinicalTrials.gov (ID: NCT03442608). 2021 Annals of Translational Medicine. All rights reserved.