Emerging evidence suggests that methadone has a specific role in the management of treatment resistant cancer-related pain.ObjectivesTo investigate the utilisation pattern, safety and efficacy of methadone prescribed as an analgesic for the management of complex cancer-related pain in an acute hospital inpatient setting.MethodsA retrospective longitudinal observational study of patients prescribed methadone as an analgesic between April 2020 and July 2021 was performed.Changes in coprescribed baseline opioid, use of breakthrough opioid analgesic, patient rated pain scores and adverse side effects were analysed.Results16 patients with complex cancer-related treatment resistant pain who were prescribed methadone were included in the study. Of the 16 patients, 14 patients had metastatic disease. Pain was classified in 14 patients as mixed nociceptive-neuropathic and in 2 patients as neuropathic. 13 patients were coprescribed methadone with a pre-established opioid. Methadone was associated with a statistically significant decrease in both opioid breakthrough analgesic by 61%±28% (p<0.001), and coprescribed opioid by 17%±12% (p=0.015). Patient rated pain scores were also significantly decreased (p<0.001).ConclusionMethadone appears to have a specific role in the management of complex cancer pain, neuropathic pain, opioid-tolerance and opioid-induced hyperalgesia, which may be attributable to N-methyl-D-aspartate receptor antagonism.