Sympathetic crashing acute pulmonary edema (SCAPE) is a medical emergency in which severe, acute elevation in blood pressure results in acute heart failure and fluid accumulation in the lungs. Without prompt recognition and treatment, the condition often progresses rapidly to respiratory failure necessitating intubation and intensive care unit (ICU) admission. In addition to non-invasive positive pressure ventilation (NIPPV), high-dose nitroglycerin (HDN) has become a mainstay of treatment; however, an optimal dosing strategy has not been established. The purpose of this study was to describe the characteristics and outcomes of patients who received an HDN infusion (≥ 100 μg/min) for the management of SCAPE in the Emergency Department (ED) of a large urban academic medical center. Outcomes were also analyzed to determine predictors of safety and efficacy including use of adjunct medication therapies. There were 67 adult patients who received HDN infusion for SCAPE from January 1, 2018 to December 31, 2018. The median (IQR) systolic blood pressure (SBP) on initiation of HDN infusion was 211 (192-233) mmHg. Patients were 63% male, 84% black, 51% had a history of heart failure (HF), and 36% had end-stage renal disease (ESRD). IV nitroglycerin (NTG) was initiated at a median (IQR) dose of 100 (100-200) mcg/min with median (IQR) peak rate in the first hour of 200 (127.5-200) mcg/min and an absolute maximum observed rate of 400 μg/min overall. 73% of patients received NIPPV, 48% sublingual (SL) or IV bolus nitroglycerin before HDN infusion, 58% loop diuretic, and 34% angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Rates of ICU admission, intubation, acute kidney injury (AKI) at 48 h, and hypotension were 37%, 21%, 13%, and 4% respectively. This is the largest to date study describing the use of an HDN infusion (≥100 μg/min) strategy for the management of SCAPE. HDN infusion may be a safe alternative strategy to intermittent bolus HDN.