BACKGROUND The PROSPECT (PROcedure SPEcific Postoperative Pain ManagemenT) Working Group is a global collaboration of surgeons and anaesthesiologists formulating procedure-specific recommendations for pain management after common operations. Total knee arthroplasty (TKA) is associated with significant postoperative pain that is difficult to treat. Nevertheless, pain control is essential for rehabilitation and to enhance recovery. OBJECTIVE To evaluate the available literature and develop recommendations for optimal pain management after unilateral primary TKA.DESIGN A narrative review based on published systematic reviews and meta-analyses, using modified PROSPECT methodology.DATA SOURCES A literature search was performed in EMBASE, MEDLINE, PubMed and Cochrane Databases, between January 2014 and December 2020, for systematic reviews and meta-analyses evaluating analgesic interventions for pain management in patients undergoing TKA.ELIGIBILITY CRITERIA Each randomised controlled trial (RCT) included in the selected systematic reviews was critically evaluated and included only if met the PROSPECT requirements. Included studies were evaluated for clinically relevant differences in pain scores, use of nonopioid analgesics, such as paracetamol and nonsteroidal anti-inflammatory drugs and current clinical relevance.RESULTS A total of 151 systematic reviews were analysed, 106 RCTs met PROSPECT criteria. Paracetamol and nonsteroidal anti-inflammatory or cyclo-oxygenase-2-specific inhibitors are recommended. This should be combined with a single shot adductor canal block and peri-articular local infiltration analgesia together with a single intra-operative dose of intravenous dexamethasone. Intrathecal morphine (100 mg) may be considered in hospitalised patients only in situations when both adductor canal block and local infiltration analgesia are not possible. Opioids should be reserved as rescue analgesics in the postoperative period. Analgesic interventions that could not be recommended were also identified.CONCLUSION The present review identified an optimal analgesic regimen for unilateral primary TKA. Future studies to evaluate enhanced recovery programs and specific challenging patient groups are needed.