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Objectives: Drug overdose death rates in the United States have increased exponentially over the past 2 decades, primarily driven by fatal opioid overdoses. To combat this epidemic, naloxone training programs have become prevalent, but still remain widely underutilized. The purpose of the current study was to assess the benefits of a brief training with differing educational approaches (individual training versus training in dyads) as well as the outcomes following overdose reversals. Methods: Persons who use opioids (N = 448) were recruited from 4 sites including treatment facilities, inpatient hospitals, and criminal justice locations over a 3-year period. Training was delivered by nonmedical personnel and focused on safe naloxone usage and recognizing overdose signs. Overdose and naloxone knowledge were assessed before and following training with a 10-item questionnaire. Participants were trained individually, in a dyad with a partner who used opioids (PO), or in a dyad with a partner who did not use opioids (PNO). Results: All training groups displayed an increased knowledge of naloxone and overdose situations following training. Approximately 11% of participants (n = 47) reported using their naloxone kit and 97.7% of those resulted in successful overdose reversals. Kits were primarily used by the trained participant on a third-party individual. Conclusions: The results of the current study substantiate the effectiveness of naloxone in reversing overdose symptoms. A brief, 15-minute naloxone training delivered by nonmedical personnel enhanced overdose knowledge and led to positive reversal outcomes. Training persons who use opioids in dyads may offer additional benefits and improve follow-up reporting.