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<h3>Introduction</h3> Pain is one of the most distressing symptoms that patients experience as they approach the end of life. Opioids remain the gold standard, but the need for alternative options is growing, especially in the face of non-opioid-responsive pain or opioid side-effects. Clonidine, initially known as a nasal decongestant and anti-hypertensive, has shown promise through its depression of the sympathetic nervous system by inhibiting noradrenaline release. It has since shown potential as an analgesic post-operatively, helping to reduce overall opioid use while providing adequate pain relief. This systematic review aimed to collate and analyse the available literature on the use of clonidine as an analgesic for palliative care patients. <h3>Methods</h3> A comprehensive literature search was performed on CENTRAL, SCOPUS, MEDLINE, EMBASE and ClinicalTrials.gov for studies assessing the use of clonidine as analgesia for patients under palliative care. 12 studies involving 194 patients were included. All studies were either case reports or case series. Clonidine was used as both monotherapy and as an adjunct through various delivery methods, including intrathecal, perineural, subcutaneous and transdermal. <h3>Results</h3> Clonidine has shown initial potential to provide adequate analgesia while reducing overall opioid usage. Notable adverse effects include orthostatic hypotension, drowsiness and hallucinations. Further insight is also required into more easily accessible delivery, such as oral, subcutaneous and transdermal routes. <h3>Conclusion</h3> This review has highlighted that clonidine may be an effective analgesic in palliative care. However, more research is required to form a stronger evidence base, with this review limited to case series and case reports, indicating that no causal conclusions can be made. More information on the extent of its use, including proposed starting doses, dose increments, easier routes of administration and the management of its adverse effects are required before more confidence can be placed in clonidine use in this population for analgesia.