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Local sustained delivery of therapeutics to the surgical site has a potential to address these complications more effectively than current clinical approaches. Given that several analgesics were shown to possess antibacterial activity, we propose here to use analgesic\u2010loaded ultra\u2010high molecular weight polyethylene (UHMWPE) as a delivery vehicle to provide antimicrobial effect after an arthroplasty. Three commonly used anesthetics, lidocaine, bupivacaine, and ropivacaine, were analyzed in order to reveal the drug with the highest antibacterial activity against methicillin\u2010sensitive <jats:italic>Staphylococcus aureus<\/jats:italic>. Having shown highest antibacterial activity in the bacterial susceptibility tests, bupivacaine was chosen to be incorporated into UHMWPE to provide antibacterial properties. Bupivacaine\u2010loaded UHMWPE possessed moderate dose\u2010dependent antimicrobial properties, decreasing the <jats:italic>S. aureus<\/jats:italic> proliferation rate by up to 70%. Biofilm formation was also substanitally inhibited during the first 9\u2009h of culture as quantified by bacterial counts and SEM. This proof\u2010of\u2010concept study is first of its kind to demonstrate that analgesic\u2010loaded UHMWPE can be used as part of a multimodal antimicrobial therapy. \u00a9 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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