Dantrolene was introduced for treatment of malignant hyperthermia. It also has antiarrhythmic properties and may thus be an alternative to amiodarone for the treatment of ventricular fibrillation (VF). Aim of this study was to compare the return of spontaneous circulation (ROSC) with dantrolene and amiodarone in a pig model of cardiac arrest. VF was induced in anesthetized pigs. After 8 min of untreated VF, chest compressions and ventilation were started and one of the drugs (amiodarone 5 mg kg-1, dantrolene 2.5 mg kg-1 or saline) was applied. After 4 min of initial CPR, defibrillation was attempted. ROSC rates, hemodynamics and cerebral perfusion measurements were measured. Initial ROSC rates were 7 of 14 animals in the dantrolene group vs. 5 of 14 for amiodarone, and 3 of 10 for saline). ROSC persisted for the 120 min follow-up in 6 animals in the dantrolene group, 4 after amiodarone and 2 in the saline group (n.s.). Hemodynamics were comparable in both dantrolene group amiodarone group after obtaining ROSC. Dantrolene and amiodarone had similar outcomes in our model of prolonged cardiac arrest, However, hemodynamic stability was not significantly improved using dantrolene. Dantrolene might be an alternative drug for resuscitation and should be further investigated.