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Bovine tuberculosis (bTB) prevalence substantially increased over the past two decades with relatively high impact on large dairy herds, raising the concern of regulatory authorities and industry stakeholders, and threatening animal and public health. Lack of resources, together with the economic and social consequences of whole-herd stamping-out, makes depopulation an impractical disease control alternative in these herds. The increase in bTB prevalence was associated with demographic and management changes in the dairy industry in Uruguay, reducing the efficacy of the current control programme (i.e. status quo) based on intradermal serial testing with caudal fold- and comparative-cervical tuberculin test-and-slaughter of reactors (CFT-CCT). Here, we aimed to assess the epidemiological effectiveness of six alternative control scenarios based on test-and-slaughter of positive animals, using mathematical modelling to infer bTB-within-herd dynamics. We simulated six alternative control strategies consisting of testing adult cattle (>1 year) in the herd every 3 months using one test (in vivo or in vitro) or a combination in parallel of two tests (CFT, interferon-gamma release assay-IGRA- or enzyme-linked immunosorbent assay). Results showed no significant differences overall in the time needed to reach bTB eradication (median ranging between 61 and 82 months) or official bovine tuberculosis-free status (two consecutive negative herd tests) between any of the alternative strategies and the status quo (median ranging between 50 and 59 months). However, we demonstrate how alternative strategies can significantly reduce bTB prevalence when applied for restricted periods (6, 12 or 24 months), and in the case of IGRAc (IGRA using peptide-cocktail antigens), without incurring on higher unnecessary slaughter of animals (false positives) than the status quo in the first 6 months of the programme (p-value < .05). Enhanced understanding bTB-within-herd dynamics with the application of different control strategies help to identify optimal strategies to ultimately improve bTB control and bTB eradication from dairies in Uruguay and similar endemic settings., (© 2020 Wiley-VCH GmbH.)