Abstract: Objective To observe the clinical efficacy of nalmefene combined with naloxone in the treatment of patients with acute severe alcoholism. Methods Totally 95 patients with acute severe alcoholism were randomly divided into control group(n=47, treated with naloxone)and observation group(n=48, treated with nalmefene and naloxone). Modified Early Warning Score(MEWS), Glasgow Coma Scale(GCS), alcohol consumption and intraoperative fluid infusion volume were compared between the two groups. Consciousness awakening rate at different time periods, time to consciousness awakening, disappearance time of unconsciousness symptoms, discharge time and incidence of adverse reactions were compared between the two groups. Results There were no significant differences in the amount of alcohol consumption, MEWS and GCS scores and intraoperative fluid infusion volume between the two groups(P>0.05). The total effective rate of the observation group was 93.75%, which was significantly higher than 78.72% of the control group(P<0.05). The time to consciousness awakening, the disappearance time of unconsciousness symptoms and the discharge time in the observation group were significantly shorter than those in the control group(P<0.05). The consciousness awakening rates at 1 hour, 2 and 3 hours in the observation group were significantly higher than those in the control group(P<0.05). The incidence of adverse reactions in the observation group was 43.75%, which was significantly lower than 65.96% in the control group(P<0.05). Conclusion Nalmefene combined with naloxone is effective and safe in the treatment of patients with acute severe alcoholism, which can shorten the therapeutic duration and promote awakening of consciousness.