This project sought to develop evidence-based guidelines for the administration of analgesics for moderate to severe pain by Emergency Medical Services (EMS) clinicians based on a separate, previously published, systematic review of the comparative effectiveness of analgesics in the prehospital setting prepared by the University of Connecticut Evidence-Based Practice Center for the Agency for Healthcare Research and Quality (AHRQ). A technical expert panel (TEP) was assembled consisting of subject matter experts in prehospital and emergency care, and the development of evidence-based guidelines and patient care guidelines. A series of nine "patient/population-intervention-comparison-outcome" (PICO) questions were developed based on the Key Questions identified in the AHRQ systematic review, and an additional PICO question was developed to specifically address analgesia in pediatric patients. The panel made a strong recommendation for the use of intranasal fentanyl over intravenous (IV) opioids for pediatric patients without intravenous access given the supporting evidence, its effectiveness, ease of administration, and acceptance by patients and providers. The panel made a conditional recommendation for the use of IV non-steroidal anti-inflammatory drugs (NSAIDs) over IV acetaminophen (APAP). The panel made conditional recommendations for the use of either IV ketamine or IV opioids; for either IV NSAIDs or IV opioids; for either IV fentanyl or IV morphine; and for either IV ketamine or IV NSAIDs. A conditional recommendation was made for IV APAP over IV opioids. The panel made a conditional recommendation against the use of weight-based IV ketamine in combination with weight-based IV opioids versus weight-based IV opioids alone. The panel considered the use of oral analgesics and a conditional recommendation was made for either oral APAP or oral NSAIDs when the oral route of administration was preferred. Given the lack of a supporting evidence base, the panel was unable to make recommendations for the use of nitrous oxide versus IV opioids, or for IV ketamine in combination with IV opioids versus IV ketamine alone. Taken together, the recommendations emphasize that EMS medical directors and EMS clinicians have a variety of effective options for the management of moderate to severe pain in addition to opioids when designing patient care guidelines and caring for patients suffering from acute pain.