Preventive infusion of antibiotics in the healthy mammary gland of cows might not be critical to prevent new infections, yet, 11 tons of medically relevant antibiotics are consumed yearly to support this practice. Here, we used next-generation sequencing and 16S rRNA gene quantitative real-time PCR to determine the effect of selective dry cow therapy on the milk microbiome and bacterial load in dairy cows. A cohort of 72 cows diagnosed negative for mastitis by an on-farm culture at dry off were randomly allocated to remain as conventional dry cow therapy (CDCT) receiving ceftiofur hydrochloride and teat sealant or selective dry cow therapy (SDCT) receiving only teat sealant. As expected at the time of enrollment (Dry off) no differences were observed for the somatic cell count (SCC) scores between treatments (P = 0.47). Selective dry cow therapy had no effects on the incidence of mastitis in the first 60 d postpartum (P = 0.46), percent of culture positive cows at d 7 postpartum (P = 0.68), and SCC scores at d 7 postpartum (P = 0.40). Firmicutes was the most abundant phylum, and Corynebacterium, Acinetobacter, and Staphylococcus, often involved in mastitis cases, were the most abundant genera across treatments and time. However, no effects of SDCT on milk microbiome and bacterial load were identified. Bacterial load was greater at 7 d postpartum than at dry off. The Chao 1 and Shannon indexes were not statistically different between CDCT and SDCT groups, regardless of time point. A negative correlation was detected between the total bacterial load, as assessed by the number of 16S rRNA gene copies, and the Shannon diversity index (r = −0.29, P < 0.01). Similar negative correlations were found when data were stratified by the occurrence of clinical mastitis, subclinical mastitis, and culture on d 7 postpartum. No correlation was found between the number of 16S rRNA gene copies and the Chao 1 richness index. Taken altogether, our findings suggest that the SDCT may help promote rational use of antimicrobials without increasing presence of pathogens in milk’s microbiome and bacterial load.