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Background. Opioids are commonly administered to patients suffering moderate to severe pain after surgery. These are most commonly delivered via patient-controlled analgesia (PCA) along with assorted non-opioid analgesics. With the current national opioid epidemic, emphasis is placed on reducing opioid administration and finding effective alternatives. While many nonopioid options exist, they have rarely been compared to each other regarding safety and efficacy for pain control. There are currently no definitive guidelines for non-opioid ‘gold standard’ alternatives. Objective. To assess the efficacy of opioid alternatives at managing moderate and severe postsurgical pain and reduce post-surgical opioid administration. Methods. This publication included studies comparing pre- and post-surgical use of any individual or combination of opioid alternatives to placebo, another opioid alternative, or combination. Included publications were systematic reviews, meta-analyses, and randomized controlled trials. Primary outcomes were pain control and opioid reduction. Safety, efficacy, and side effects such as nausea/vomiting were also assessed. Results. Due to the broad scope of the subject being examined, several variables were compared across different modalities and forms of treatment. Of the monotherapies studied, alpha-2 agonists, COX-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and paracetamol were the most efficacious at reducing morphine consumption post-surgery. The publications also found that combining acetaminophen and an NSAID reduced pain and provided opioid-sparing effects. OPIOID ALTERNATIVES POST-SURGERY v Conclusion. Several monotherapies were found to be effective opioid alternatives. Of these, COX-2 inhibitors and NSAIDs showed the most evidence as effective treatments for moderate to severe post-surgical pain and reducing post-surgical opioid consumption. Additionally, combination therapy of acetaminophen plus an NSAID was found to have the greatest morphine reduction. However, lack of knowledge of the side effects of combination therapies prevent their broad implementation in clinical practice. Other monotherapies studied were paracetamol, glucocorticoids, pregabalin, gabapentin, and flupirtine. These are not as strongly recommended because of their lack of availability (as with flupirtine) or because they were not as effective. Overall, COX-2 inhibitors and NSAIDs were the safest and most effective monotherapy alternatives to opioid use