A mathematical model was used to estimate the efficacy of postmilking teat disinfection from observations in split-udder trials with natural exposure. Data were studied from an outbreak of Staphylococcus aureus IMI during a split-udder trial in a commercial herd with low SCC. The efficacy of postmilking teat disinfection was similar when calculated based on incidence density rates or on transmission rates of IMI in dipped and control quarters. If, however, first and subsequent S. aureus IMI in a cow were not assumed to be independent and were therefore treated separately in the models, the efficacy of post-milking teat disinfection was calculated as being higher with the modeling procedure. The analysis using mathematical modeling, which includes the effect of the number of existing IMI on the number of new IMI, is presented and discussed. This analysis also allows estimation of the basic reproduction ratio. The impact of postmilking teat disinfection on transmission of pathogens is quantified, and proposals for additional preventive measures can be generated. We concluded that efficacy estimations from split-udder trials, assuming quarters to be independent observations, might underestimate the effect of postmilking teat disinfectants on udder pathogens.