Purpose: A pilot project using epinephrine at the scene under medical control is currently underway in Korea. This study aimed to determine whether prehospital epinephrine administration is associated with improved survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients who received epinephrine during cardiopulmonary resuscitation (CPR) in the emergency department. Materials and Methods: This retrospective observational study used a nationwide multicenter OHCA registry. Patients were classified into two groups according to whether they received epinephrine at the scene or not. The associations between prehospital epinephrine use and outcomes were assessed using propensity score (PS)-matched analysis. Multivariable logistic regression analysis was performed using PS matching. The same analysis was repeated for the subgroup of patients with non-shockable rhythm. Results: PS matching was performed for 1084 patients in each group. Survival to discharge was significantly decreased in the patients who received prehospital epinephrine [odds ratio (OR) 0.415, 95% confidence interval (CI) 0.250–0.670, p<0.001]. However, no statistical significance was observed for good neurological outcome (OR 0.548, 95% CI 0.258–1.123, p=0.105). For the patient subgroup with non-shockable rhythm, prehospital epinephrine was also associated with lower survival to discharge (OR 0.514, 95% CI 0.306–0.844, p=0.010), but not with neurological outcome (OR 0.709, 95% CI 0.323–1.529, p=0.382). Conclusion Prehospital epinephrine administration was associated with decreased survival rates in OHCA patients but not statistically associated with neurological outcome in this PS-matched analysis. Further research is required to investigate the reason for the detrimental effect of epinephrine administered at the scene.