The number of opioid overdoses (ODs) has risen in recent years and has become more complex due to the co-involvement of both prescription and illicit opioid drug use. Provisional programs for take-home naloxone (a medication designed to rapidly reverse opiate OD symptoms) kits have been distributed to combat this potentially fatal epidemic. Although there is strong evidence to support the efficacy of naloxone in the reversal of opiate OD, there is limited evidence to support the efficacy of take-home naloxone (THN) kits. The purpose of this evidence-to-practice review was to summarize a systematic review on the efficacy of THN programs. The authors aimed to include studies of THN programs that both trained opioid users in OD prevention and reported on OD outcomes. The Bradford Hill criteria (strength of association, temporality, consistency, specificity, dose-response relationship, biological plausibility, coherence, experimental evidence, and analogy) and five additional criteria (measure cost-effectiveness, absence of negative consequences, feasibility of implementation/expansion/ coverage, unanticipated benefits, and special populations) was used as dependent variables to determine the impact of public health intervention where randomized control trials (RCTs) are not ethically feasible or operationally practical. All 22 studies included provided empirical support using the Bradford Hill Criteria for community based THN programs. Despite being unable to deduce whether death would have occurred without the administration of THN, the studies combined accounted for an estimated 2316 successful opioid OD reversals. Thus, there is a strong association between THN administration and overdose survival. Additionally, there was a low rate of adverse events: withdrawal symptoms (2.8%), vomiting (2.2%), agitation (2.1%), seizures (0.1%). Consequently, we recommend that athletic trainers include opioid crisis management equipment and procedures in a site-specific policies manual. Clinical relevance is highly dependent on patient population and geographic location, considering 90% of reversed ODs were heroin induced. Application to individuals in organized sport is minimal, but nonetheless, individuals who are prescribed opioids for pain management should be candidates for THN programs. Athletic trainers and guardians of minors prescribed opioid medications should be educated on dispensing medication, best practices for opioid crisis management, and distribution of naloxone/THN.