To investigate the effect of erythropoietin for the management of postresuscitation myocardial dysfunction following asphyxia-induced cardiac arrest. Male adult Wistar rats were used for the prospective controlled animal study. Asphyxia-induced cardiac arrest was performed by turning-off the ventilator and clamping the endotracheal tube. Cardiopulmonary resuscitation with an intravenous injection of 0.01 mg/kg epinephrine and mechanical ventilation were started after 6.5 minutes of asphyxia. The resuscitated animals received either erythropoietin (5000 U/kg) or equivalent volume of 0.9% saline as placebo intravenously 3 minutes after return of spontaneous circulation. The erythropoietin treatment produced better left ventricular dP/dt40 and -dP/dt in the invasive hemodynamic measurements, and left ventricular fraction shortening by echocardiography. Administration of erythropoietin also improved three days survival among those successfully resuscitated. The molecular effects of erythropoietin were shown by activation of its down streaming Akt and ERK 42/44 signaling pathways. EPO has the potential to improve postresuscitation myocardial dysfunction and short term survival in rats after asphyxia-induced cardiac arrest.