Background: The optimal analgesic strategy for patients undergoing donor hepatectomy is not known and the potential short- and long-term physical and psychological consequences of complications are significant. Objectives: To identify whether a multimodal approach to pain of the donor intraoperatively enhances immediate and short-term outcomes after living liver donation, and to provide international expert panel recommendations. Data sources: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. Methods: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO 2021 CRD42021260699. Results: Nine studies assessing multi-modal analgesia strategies were included in a qualitative assessment. Interventions included local, regional, and neuro-axial anesthetic techniques, pharmacological intervention (NSAIDs, COX-2 inhibitors, ketamine, dexmedetomidine, and lidocaine), and acupuncture. Overall, there was a significant (40%) reduction in opioid requirement on day 1 and a significant reduction in pain scores in the intervention vs control groups. Significant reductions in either length of stay or post-operative complications were demonstrated in four of nine studies. Conclusions: Opioid use for patients undergoing donor hepatectomy is likely to impact both their short- and long-term outcomes. To reduce post-operative pain scores, shorten length of hospital stay, and promote earlier post-operative return of bowel function, we recommend that multi-modal analgesia be offered to patients undergoing living donor hepatectomy. Further research is required to confirm which multi-modal techniques are most associated with enhanced recovery in living liver donors.