Background: The opioid epidemic is a health crisis in the United States. Physicians contribute to this problem by overprescribing opioids. Ambulatory hand surgery (AHS) is common in the United States and associated with overprescribing of opioids. Education and guidance regarding the effectiveness of nonopioid compared with opioid interventions for pain management following ambulatory hand procedures are lacking. We assessed the current literature to suggest evidence-based protocols for postoperative analgesia. Methods: A systematic review was performed using PubMed, Web of Science, and Cochrane Library. Studies comparing nonopioid with opioid treatments for pain management following AHS were identified. Studies investigating opioid-sparing strategies after AHS were also identified. Evidence was examined to determine efficacy of nonopioid interventions and to provide recommendations for optimal nonopioid protocols and opioid-sparing strategies. Results: A total of 510 studies were identified in the search with 18 meeting inclusion criteria. High-level evidence demonstrated efficacy of nonopioid interventions for pain management following AHS (levels I and II evidence). Results provided evidence-based guidelines for recommendations of nonopioid treatment protocols and opioid-sparing strategies (levels I and II evidence). Conclusions: Our review demonstrated nonopioid interventions are adequate in multiple aspects of pain management compared with opioid treatments. Recommendations were established for two nonopioid treatment protocols, and for an opioid-sparing intervention (levels I and II evidence). The evidence provided in this review should be strongly considered for pain management guidance following AHS and provides a means to decrease opioid overprescribing in the United States.