Highlights • Certain variables in severe spontaneous supratentorial intracerebral hemorrhage are predictors of an increased risk for the development of BD. • This information could be useful in the ever-growing search to find potential organ donors. Abstract Objective This study sought to identify clinical variables that may contribute to the development of brain death (BD) in patients with severe supratentorial intracerebral hemorrhage (ICH). Methods A prospective observational study was carried out from 2012 to 2014 and included patients with severe supratentorial ICH (Glasgow Coma Score ≤ 8). Exclusion criteria included aneurysmal or traumatic hemorrhage origin and hemorrhagic transformation of previous ischemic stroke. The following data were collected: clinical variables (past medical history, clinical severity at admission), head computed tomography scan findings, laboratory data, neurosurgical procedures, and immediate complications. Univariate tests and logistic regression analyses were performed to assess the predictive ability of these variables and identify patients at high risk of progression to BD. Results A total of 140 patients with severe supratentorial ICH (median age, 60; 68.6% male) were included. Of these 140 cases, 24 progressed to BD. In the multivariate analysis, the following variables were independently associated with BD outcome after supratentorial ICH: a history of arterial hypertension (odds ratio [OR], 11.254; P = .003), anticoagulant therapy (OR, 3.561; P = .050), presence of photomotor impairment at admission (OR, 7.095; P = .001), rebleeding after supratentorial ICH (OR, 5.613; P = .010), and no neurosurgical hematoma evacuation in ICH (OR, 8.314; P = .001). Conclusions Certain clinical variables are predictive of an increased risk for BD development after supratentorial ICH. This information would be useful for transplant coordinators, permitting early identification of at-risk patients and increasing the availability of potential donors.