The selection of antimicrobial agents for the treatment of mastitis has often been based on results of in vitro susceptibility testing. However, the results of in vitro susceptibility tests have been shown to be poor predictors of treatment outcomes. The objective of this study was to determine if an association existed between results of antimicrobial susceptibility tests and outcomes of mastitis caused by gram-positive pathogens recovered from quarters that received treatment with cephapirin sodium. Mastitis pathogens were obtained from a multi-site clinical trial that evaluated the bene-fits of using an onfarm culturing system. Target patho-gens (n = 187) comprised coagulase-negative staphylocci (65%), Streptococcus spp. (14%), other pathogens (12%), and Staphylococcus aureus (11%), which were recovered from quarters that received treatment using cephapirin sodium. The antimicrobial susceptibility profile to cephapirin was determined using the broth micro-dilution technique. The overall bacteriological cure rate achieved by cephapirin treatment was 82%. Bacteriological outcomes (cure or treatment failure) were not associated with pathogen type. A recurrent case of mastitis was observed in 10 quarters classified as cures and 3 quarters classified as treatment failures. Recurrence of mastitis was not associated with bacteriological outcomes or susceptibility test results. In vitro susceptibility to cephapirin was exhibited by 94.8 and 91.2% of pathogens recovered from quarters classified as cures and treatment failures, respectively. Bacteriological outcomes of mastitis treated using cephapirin were not associated with in vitro susceptibility test results or in vitro minimum inhibitory concentration values. In this population, there was an 82% probability of treatment success when the isolate was susceptible but only a 27% probability of treatment failure when the isolate was resistant. Based on this research, results of in vitro susceptibility tests should not be used as the primary guide for treatment decisions regarding intramammary cephapirin sodium.