Extracorporeal membrane oxygenation (ECMO) is one of the primary reasons systemic hypertension is experienced in hospitalized neonates. Commonly used antihypertensive agents have resulted in significant adverse effects in neonatal and pediatric populations. Nicardipine is a desirable option because of its rapid and titratable antihypertensive properties and low incidence of adverse effects. However, data for use in neonatal ECMO are limited. We conducted a retrospective review of patients less than 44 weeks post-menstrual age who received a nicardipine infusion for first-line treatment of systemic hypertension while on ECMO at our institution between 2010 and 2016. Systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressures were evaluated for 48-h after nicardipine initiation. Eight neonates received a nicardipine infusion while on ECMO during the study period. Nicardipine was initiated at a mean dose of 0.52 ( ± 0.22) mcg/kg/min and titrated to a maximum dose of 1.1 ( ± 0.85) mcg/kg/min. The median duration of nicardipine use was 51 (range 4–227) hours. Significant decreases in SBP, DBP, and MAP occurred within one hour of initiation of nicardipine and were sustained through the majority of the 48-h evaluation period. No patients experienced hypotension. Prospective studies are warranted to evaluate the optimal dose, safety, and efficacy of nicardipine in neonates who require ECMO.