Summary: With the growing opioid epidemic, plastic surgeons are being encouraged to transition away from reliance on postoperative opioids. However, many plastic surgeons hesitate to use nonopioid analgesics such as nonsteroidal antiinflammatory drugs and local anesthetic blocks because of concerns about their safety, particularly bleeding. The goal of this systematic review is to assess the validity of risks associated with nonopioid analgesic alternatives. A comprehensive literature search of the PubMed and MEDLINE databases was conducted regarding the safety of opioid alternatives in plastic surgery. Inclusion and exclusion criteria yielded 34 relevant articles. A systematic review was performed because of the variation between study indications, interventions, and complications. Thirty-four articles were reviewed that analyzed the safety of ibuprofen, ketorolac, celecoxib, intravenous acetaminophen, ketamine, gabapentin, liposomal bupivacaine, and local and continuous nerve blocks after plastic surgery procedures. There were no articles that showed statistically significant bleeding associated with ibuprofen, celecoxib, or ketorolac. Similarly, acetaminophen administered intravenously, ketamine, gabapentin, and liposomal bupivacaine did not have any significant increased risk of adverse events. Nerve and infusion blocks have a low risk of pneumothorax. Limitations of this study include small sample sizes, different dosing and control groups, and more than one medication being studied. Larger studies of nonopioid analgesics would therefore be valuable and may strengthen the conclusions of this review. As a preliminary investigation, this review showed that several opioid alternatives have a potential role in postoperative analgesia. Plastic surgeons have the responsibility to lead the reduction of postoperative opioid use by further developing multimodal analgesia.