Pure autonomic failure (PAF) is characterized by neurogenic orthostatic hypotension and marked blood pressure (BP) lability. Droxidopa is widely used for symptomatic management and is generally well tolerated. We report a 60-year-old woman with advanced PAF who developed a hypertensive emergency with vasogenic cerebral edema shortly after initiation of low-dose droxidopa. This case highlights that severe hypertensive complications with reversible cerebral edema may occur even during low-dose droxidopa initiation in vulnerable patients with advanced autonomic dysfunction, underscoring the need for cautious dose titration and close BP monitoring.