The objective of the study was to evaluate premilking teat disinfectant efficacy with the use of a novel diagnostic protocol against a positive control. The evaluation of efficacy was based on establishing noninferiority of a new premilking teat disinfectant compared with an existing premilking teat disinfectant. Approximately 200 cows were randomly allocated to 1 of 2 groups. Study personnel were blinded as to cow allocation and identification of the premilking disinfectants. Quarters were disinfected using a dip cup before milking with either the control or experimental product. The disinfectant was left on the teat for approximately 30 s before being wiped off in preparation for milking. Quarter-level bacteriological infection status was established at the beginning of the study and quarter milk samples were collected biweekly thereafter. Bacteriological analyses were performed only when somatic cell counts in milk samples crossed a parity-specific threshold. Poisson regression models were used to analyze data. The difference in the rate of new intramammary infections was small and the upper bound of the 95% confidence interval of the rate difference was smaller than a predefined noninferiority limit. Based on the observed difference in new intramammary infections rate between the experimental and control product, it was concluded that the experimental disinfectant was not inferior compared with the positive control. The protocol used in this study proposes a valid and economically attractive methodology to evaluate the efficacy of teat disinfectants relative to a positive control.