Maintaining udder health is the primary indication for antimicrobial use (AMU) in dairy production, and modulating this application is a key factor in decreasing AMU. Defining the optimal AMU and the associated practical rules is challenging since AMU interacts with many parameters. To define the trade-offs between decreased AMU, labor and economic performance, the bioeconomic stochastic simulation model DairyHealthSim (DHS)© was applied to dairy cow mastitis management and coupled to a mean variance optimization model and marginal abatement cost curve (MACC) analysis. The scenarios included three antimicrobial (AM) treatment strategies at dry-off, five types of general barn hygiene practices, five milking practices focused on parlor hygiene levels and three milk withdrawal strategies. The first part of economic results showed similar economic performances for the blanked dry-off strategy and selective strategy but demonstrated the trade-off between AMU reduction and farmers' workload. The second part of the results demonstrated the optimal value of the animal level of exposure to AM (ALEA). The MACC analysis showed that reducing ALEA below 1.5 was associated with a EUR 10,000 loss per unit of ALEA on average for the farmer. The results call for more integrative farm decision processes and bioeconomic reasoning to prompt efficient public interventions.