On many pig farms, growing pigs are mass-medicated for short periods with antimicrobial drugs through their drinking water for metaphylaxis and to treat clinical disease. We conducted a series of four prospective observational cohort studies of routine metaphylactic in-water antibiotic dosing events on a commercial pig farm, to assess the concentration of antimicrobial available to pigs throughout a building over time. Each dosing event was conducted by the farm manager with a differently designed looped water distribution system (WDS). We found that the antimicrobial concentration in water delivered to pigs at drinkers in each pen by a building’s WDS over time was profoundly influenced by the design of the WDS and the pigs’ water usage and drinking pattern, and that differences in the antimicrobial concentration in water over time at drinkers throughout a building could be eliminated through use of a circulator pump in a looped WDS. We also used a hydraulic WDS modelling tool to predict the antimicrobial concentration at drinkers over time during and after a dosing event. Our approach could be used to evaluate alternative in-water dosing regimens for pigs in a specific building in terms of their clinical efficacy and ability to suppress the emergence of antimicrobial resistance, and to determine the optimal regimen. The approach is applicable to all additives administered through drinking water for which the degree of efficacy is dependent on the dose administered.