The purpose of this study was to determine the effects of epinephrine in insulin-treated diabetics (DM) compared with nondiabetic (ND) controls during cardiopulmonary resuscitation (CPR). A retrospective analysis from a multicenter study of out-of-hospital cardiac arrest included 62 DM and 1,151 ND. Outcome parameters included return of spontaneous circulation (ROSC), blood pressure (BP), emergency department admissions (EDA), hospital admissions (HA), and hospital discharge (DC). In DM treated with standard-dose epinephrine (SDE), there were trends toward improved ROSC, BP, EDA, and HA compared with ND. DC was not different. With high-dose epinephrine (HDE) these outcomes were not different. Comparison of the outcomes of DM given SDE versus those given HDE were not different. However, none of the DM given HDE (n = 24) were discharged from the hospital. These results suggest that DM may have improved resuscitation rates with SDE and may be adversely affected with HDE. Larger prospective studies are needed to confirm these findings.