ObjectiveThis study aims to review opioid prescribing changes for pain management in head and neck cancer (HNC) surgery patients, given the recent focus on Enhanced Recovery After Surgery protocols.Data SourcesMEDLINE, Embase, and CENTRAL, covering 1998 to 2023.Review MethodsWe selected studies that evaluated opioid prescribing patterns post-major HNC surgery in various settings, including tertiary care hospitals and community hospitals. Primary outcomes considered were prevalence and patterns of opioid use post-surgery, as well as related outcomes such as chronic use and side effects.ResultsOf 1278 abstracts, 24 studies involving 17,027 patients from the United States, China, and Canada met inclusion criteria. Quality was assessed using the MINORS scale, with an average score of 9.9 for non-comparative studies and 20.0 for comparative studies. Persistent opioid use post-surgery, defined as ongoing prescriptions 90 days after treatment, was noted in 15.4% to 64% of patients. Two studies reported adverse events, with up to 16% of patients experiencing side effects. Risk factors for chronic use included preoperative opioid use, tobacco use, higher cancer stage, adjuvant treatment, and demographic factors. Correlations were found between larger opioid prescriptions and shorter survival in advanced cancers. There was notable variability in patient-reported pain control.ConclusionPersistent opioid use post-HNC surgery is common, with variable efficacy and risk of adverse effects. Tailoring pain management to individual risk factors and focusing on multimodal analgesia could reduce the risks of continued opioid use. Future prospective studies are required to identify optimal pain management strategies.