Abstract The transmission of antimicrobial resistance (AMR) between animals, their environment, food and humans is a complex issue and more evidence is needed to strengthen current understanding. Models of disease transmission within commercial farm environments can provide further insight to the on-farm transmission dynamics of AMR between animals and their environment, as well as predict the effect of various on-farm interventions. Previous generic models indicate that ESBL resistant bacterial populations may be self-sustaining through horizontal and vertical gene transfer, even in the absence of antimicrobial pressure. However, models focusing purely on the biochemical aspects fail to incorporate the complicated host population dynamics which occur within a farm environment. As part of the One Health European Joint Programme (OHEJP) joint research project RaDAR (risk and disease burden of antimicrobial resistance), we present a model framework for incorporating pharmacokinetic-pharmacodynamic (PKPD) models; exploring the complex host/gut bacteria interplay, with on-farm models of disease transmission in order to predict the infection dynamics on pig farms. The model is designed to be adaptable for the simultaneous transmission of multiple bacteria and resistant strains. In addition, the model incorporates the faecal excretion (and subsequent ingestion) of antimicrobial residues from pigs that have been treated with antibiotics. The model predicted that after introduction of ESBL E. coli onto a pig farm, the disease is likely to persist on the farm for more than a year leading to a high level of carriage (13.7%, 5th and 95th percentiles: 0-53.1) and faecal shedding in slaughter–age pigs. Isolation of pigs in sick pens for the duration of their antibiotic treatment reduced the number of positive batches whereas an enhanced cleaning and disinfectant (C&D) protocol reduced the within herd prevalence. Both interventions were able to reduce the number of pigs shedding more than 2log10 ESBL E. coli from 8.5% (5th and 95th percentiles: 0-29.2) in the baseline scenario, to 0.07% (5th and 95th percentiles: 0-0.3) when sick pens were used and 3.4% (5th and 95th percentiles: 0-16.5) when an enhanced C&D protocol was applied. A combination of the two interventions was most effective at reducing overall prevalence (5.6%, 5th and 95th percentiles: 0-40.6). The results suggest that actions targeted towards preventing or removing the colonisation of AMR bacteria within themicrobiome of pigs are more likely to be effective than steps to remove contamination levels within the pen environment.