Objective: To evaluate the effectiveness of epinephrine, compared with control treatments, on survival at admission, ROSC, survival to discharge, and a favorable neurologic outcome in adult patients during OHCA. Data source: MEDLINE and PubMed from inception to August 2018. Study selection: Randomized controlled trials (RCTs) on adult patients after out-of-hospital cardiac arrest (OHCA) treated with epinephrine versus controls. Data extraction: Independent, double-data extraction; risk of bias assessment with Cochrane Collaboration's criteria. Data synthesis: 15 RCTs representing 20,716 OHCA adult patients. When epinephrine was compared with a placebo/no drugs, survival to hospital discharge (RR: 1.34, 95% CI: 1.08-1.67), ROSC (RR: 2.03, 95% CI: 1.18-3.51) and survival to hospital admission (RR: 2.04, 95% CI: 1.22-3.43) were increased, but favorable neurologic outcome was not significantly different (RR: 1.22, 95% CI: 0.99-1.51). Patients treated with the high-dose epinephrine (HDE) had a higher rate of ROSC (standard-dose epinephrine (SDE) versus HDE, RR: 0.85, 95% CI: 0.74-0.97, p = 0.01) and increased survival to hospital admission (SDE versus HDE, RR: 0.86, 95% CI: 0.75-0.99, p = 0.04) compared with those treated with SDE. No considered treatments improved the neurological outcome after OHCA. Conclusions: In OHCA, standard or high doses of epinephrine should be used because they improved survival to hospital discharge. There was also a clear advantage of using epinephrine over a placebo or no drugs in the considered outcomes.