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Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder characterized by nonspecific acute neurological signs and symptoms combined with typical imaging findings. It usually has a favorable prognosis but can occasionally be complicated by severe and life-threatening manifestations. Malignant PRES is the most severe form of this condition, defined by coma, refractory intracranial hypertension, and radiological evidence of cerebral edema or hemorrhage associated with a mass effect. We report a case of a 53-year-old woman with high-risk myelodysplastic neoplasm with increased blasts-2 who underwent allogeneic hematopoietic stem cell transplantation. The post-allograft period was complicated by grade III acute graft-versus-host disease, which required intensified immunosuppression with high-dose prednisolone and therapeutic doses of cyclosporine. Eighty-three days after transplantation, the patient was admitted to the emergency department with acute neurological symptoms. Rapid development of coma and clinical signs of intracranial hypertension, refractory to osmotic therapy with mannitol and hypertonic saline, prompted an emergency decompressive craniectomy. Magnetic resonance imaging confirmed the diagnosis of malignant PRES. Withdrawal of cyclosporine, mycophenolate mofetil, and voriconazole, along with intensive supportive management in the neurocritical care unit, resulted in complete neurological recovery.