INTRODUCTION: Vasopressors are commonly used for calcium channel blocker (CCB)-induced cardiogenic shock after calcium and high-dose insulin (HDI). Vasopressor therapy is frequently used in combination with HDI to increase blood pressure and improve outcome. However, no studies have compared the efficacy of HDI to the combination of a vasopressor and HDI in dihydropyridine overdose. We conducted a study to compare the efficacy of HDI to phenylephrine (PE) plus HDI in a porcine model of dihydropyridine toxicity. METHODS: Cardiogenic shock was induced by administering a nifedipine (NP) infusion of 0.0125 mcg/kg/min until a point of toxicity, defined as a 25% decrease in the baseline product of mean arterial pressure (MAP) x cardiac output (CO). Each arm was resuscitated with 20 mL/kg of saline (NS). The nifedipine infusion continued throughout a 4-h resuscitation protocol. The HDI group was titrated up to 10 units/kg/h of insulin and the HDI/PE group was titrated up to a dose of HDI 10 units/kg/h plus PE 3.6 mcg/kg/min. RESULTS: No baseline differences were found among groups including time to toxicity. Survival was not different between the HDI and HDI/PE arms. When comparing the HDI to the HDI/PE arm no differences were found for cardiac index (CI) (p = 0.06), systemic vascular resistance (p = 0.34), heart rate (HR) (p = 0.95), mean arterial pressure (p = 0.99), pulmonary vascular resistance (PVR) (p = 0.07), or base excess (p = 0.36). CONCLUSION: In this model of nifedipine-induced cardiogenic shock, the addition of PE to HDI therapy did not improve mortality, cardiac output, blood pressure, systemic vascular resistance (SVR), or base excess.