Context: The present systematic review and meta-analysis aims to perform an extensive search in databases to compare the efficacy of the intranasal administration of naloxone with its intramuscular/intravenous administration in the pre-hospital management of opioid overdose.Evidence acquisition: This meta-analysis included controlled trials conducted on the efficacy of naloxone administration in the pre-hospital management of opioid overdose. A search was carried out in electronic databases on relevant articles published by the end of ۲۰۱۸. After data collection, analyses were performed in STATA ۱۴.۰ software and the efficacy and side-effects of the two administration routes of naloxone, i.e. intranasal and intramuscular/intravenous, were compared. An overall effect size with ۹۵% confidence interval (۹۵% CI) was provided for each section. Results: Eventually, data from six studies were included in this meta-analysis. The success rate of the intranasal and intramuscular/intravenous administration of naloxone in the management of opioid overdose in prehospital settings was ۸۲.۵۴% (۹۵% CI: ۵۷.۹۷ to ۹۷.۸۹%) and ۸۰.۳۹% (۹۵% CI: ۵۷.۳۸ to ۹۶.۰۴%), respectively.There was no difference between injectable (intramuscular/intravenous) naloxone and intranasal naloxone in the pre-hospital management of opioid overdose (Odds Ratio=۱.۰۱; ۹۵% CI: ۰.۴۲ to ۲.۴۳; P=۰.۹۸). The onset of action of intranasal naloxone, however, was slightly longer than injectable naloxone (Standardized Mean Difference=۰.۶۳; ۹۵% CI: ۰.۰۷ to ۱.۱۹; P=۰.۰۳). Additionally, the odds of needing a rescue dose was ۲.۱۷ times higher for intranasal naloxone than intramuscular/intravenous naloxone (OR=۲.۱۷; ۹۵% CI: ۱.۵۳ to ۳.۰۹; P<۰.۰۰۰۱). The prevalence of major side-effects was non-significant for both intranasal (۰.۰۰%) and intramuscular/intravenous (۰.۰۵%) routes of naloxone administration and there was no difference in the prevalence of major (OR=۱.۱۸; ۹۵% CI: ۰.۳۸ to ۳.۶۹; P=۰.۷۷۷) and minor (OR=۰.۶۴; ۹۵% CI: ۰.۱۷ to ۲.۳۴;P=۰.۴۹۷) side-effects between the two routes.Conclusion: The present meta-analysis demonstrated that intranasal naloxone is as effective as injectable naloxone in the pre-hospital management of opioid overdose complications. Consequently, intranasal naloxone may be an appropriate alternative to injectable naloxone.