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As outpatient (day-case) surgery had continued to grow throughout the world, many more complex and potentially painful procedures are being routinely performed in the ambulatory setting. Opioid analgesics, once considered the standard approach to preventing acute postoperative pain, are being replaced by a combination of nonopioid analgesic drugs with diverse modes of action as part of a multimodal approach to preventing pain after ambulatory surgery. This review will provide an update on the topic of multimodal pain management for ambulatory (day-case) surgery.Efficacy of multimodal analgesic regimens continues to improve; opioid analgesics are increasingly taking on the role of ‘rescue analgesics’ for acute pain after day-case surgery. The use of multimodal analgesia is rapidly becoming the ‘standard of care’ for preventing pain after ambulatory procedures at most surgery centers throughout the world.This article discusses recent evidence from the peer-reviewed literature regarding the role of local anesthetics, NSAIDs, gabapentinoids, and acetaminophen, as well as alpha-2 agonists, ketamine, esmolol, and nonpharmacologic approaches (e.g., transcutaneous electrical stimulation) as parts of multimodal pain management strategies in day-case surgery.