Dairy farm use of antimicrobial drugs (AMD) is a risk for the selection of antimicrobial resistance (AMR); however, these resistance dynamics are not fully understood. A cohort study on two dairy farms enrolled 96 cows with their fecal samples collected three times weekly, for the first 60 days in milk. Enterobacteriaceae were enumerated by spiral plating samples onto MacConkey agar impregnated with 0, 1, 8, 16 and 30 µg/mL ceftiofur. Negative binomial regression analyzed AMR over time. The continuum of ceftiofur concentrations permitted estimation of the minimum inhibitory concentration (MIC) and analysis using interval regression. The most common systemic AMD was ceftiofur, administered in 94% of treatments (15/16 cows). Enterobacteriaceae did not grow in 88% of samples collected from non-AMD treated cows at 8 µg/mL ceftiofur. Samples from AMD treated cows had peak counts of resistant Enterobacteriaceae during AMD treatment and returned to baseline counts by 3-4 days post-treatment at 8 µg/mL. Sensitive Enterobacteriaceae (0-1 µg/mL ceftiofur) were reduced below pre-treated levels for 29-35 days post-AMD treatment. Population MIC peaked during AMD treatment and returned to baseline levels by 7-8 days. We conclude that the effect of systemic ceftiofur on the resistance of Enterobacteriaceae in early lactation dairy cows was limited in duration.