Background: Antimicrobial resistance (AMR) is a major threat to global health. By 2050, it is forecast that AMR will cause 10 million deaths and cost 100 trillion USD annually. Point-of-care tests (POCTs) may represent a cost-effective approach to reduce AMR., Objectives: We systematically reviewed which POCTs addressing AMR have undergone economic evaluation in primary and secondary healthcare globally, how these POCTs have been economically evaluated, and which are cost-effective in reducing antimicrobial prescribing or the burden of AMR. Clinical cost-effectiveness was additionally addressed., Methods: This systematic review, accordant with PRISMA guidelines, was pre-registered on PROSPERO (CRD42022315192). MEDLINE, PubMed, Embase, Cochrane Library, and Google Scholar were searched from 2000 to 2023 for relevant publications. Quality assessment was performed using the Consensus of Health Economic Criteria., Results: The search strategy identified 1421 studies, of which 20 met the inclusion criteria. The most common POCTs assessed were for respiratory infections (n = 10), STIs (n = 3), and febrile patients in low- and middle-income countries (n = 3). All studies assessed costs from a healthcare provider perspective; five additionally considered the societal cost of AMR.Eighteen studies identified POCT strategies that reduced antimicrobial prescribing. Of these, 10 identified POCTs that would be considered cost-effective at a willingness-to-pay (WTP) threshold of £33.80 per antibiotic prescription avoided. Most POCT strategies improved clinical outcomes (n = 14); the remainder were clinically neutral., Conclusions: There is evidence that some POCTs are cost-effective in reducing antimicrobial prescribing, with potential concomitant clinical benefits. Such interventions-especially CRP POCTs in both high- and low-income settings-merit further, large-scale clinical evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)