Background <p>Total knee arthroplasty (TKA) is associated with moderate to severe postoperative pain. Pain control is crucial for rapid mobilisation and reduces side effects as well as the length of hospital stay. In this context, a variety of multimodal pain control regimes show good pain relief, including several nerve blocks, iPACK and local infiltration analgesia (LIA). To compare the analgesic potency of LIA and the combination of continuous femoral nerve block + sciatic single-shot nerve block under general anaesthesia, we conducted a prospective, randomized, controlled, non-blinded single-centre study.</p> Method <p>&#xa0;139 ASA I-III Patients were enrolled in the study, randomised into two groups. The LIA group received an intra- and periarticular infiltration containing a mix of ropivacaine 0,2%, adrenaline and ketorolac, followed by an infusion of the same mixture for 48&#xa0;h via an intraarticular catheter. The patients in the FEM group received a combination of continuous femoral nerve block with a catheter using 30&#xa0;ml prilocaine 1% and ropivacaine 0,2% plus a single-shot sciatic nerve block via an antero-medial approach (landmark-based technique) with 20&#xa0;ml ropivacaine 0,75%. Postoperative pain scores were analysed during the first two postoperative days, as well as opioid consumption, the degree of knee movement and the occurrence of infections in both groups applying the Wilcoxon-Mann-Whitney test, Friedman chi-square test and the Log-rank-test.</p> Results <p>No significant difference in pain scores, opioid consumption, time to first rescue analgesia, knee range of motion, age, height, weight and ASA could be detected. No severe side effects, such as secondary bleeding or infections, were reported.</p> Conclusion <p>Both techniques are well established, provide equal pain relief for TKA and support early postoperative mobilisation.</p> Trial Registration <p>DRKS 00027145 08/12/2021. “retrospectively registered”.</p>