Abstract Background Due to financial issues and the rise in antimicrobial resistance, updating dry cow therapy (DCT) methods is still being researched by scientists worldwide. This investigation aimed to evaluate a new method of selective treatment by choosing an appropriate dry cow antimicrobial product for each cow based on the individual culture and antibiogram results and examining its effects on clinical and subclinical mastitis indices, cure rate, new infection rate, and milk yield during the first 30 days in milk (DIM). Materials and methods: A total of 291 Holstein dairy cows were selected from three herds. These cows had a somatic cell count (SCC) > 200,000 (cells/mL) just before drying off, had positive composite milk culture results, and were gradually dried over five days. The milk samples were taken before drying off and on the day after calving (1DIM) for microbial culture evaluation, as well as 3 days before drying off and between 3 and 7 days postpartum to evaluate SCC. The cows were randomly divided into two groups of control (n = 151) and treatment (n = 140). The control group included cows that were treated with dry cow antimicrobial products regardless of the pathogens involved in mammary infection, and the treatment group contained cows that received dry cow antimicrobial products based on the type of pathogen isolated during culture and the antibiogram results before drying off. Results: The results revealed that the cure rate in the treatment group was significantly better than that in the control group (P = 0.0006). In addition, the rate of new intramammary infections (IMI, P = 0.0006) and the rate of clinical mastitis (P = 0.015) decreased in the first 30 DIM in the treatment group. Nevertheless, the SCC and milk yield at the onset of subsequent lactation did not differ significantly between the control and treatment groups (P > 0.05). Conclusion: According to the findings of our study, based on individual milk culture and antibiogram results, selectively treating cows with appropriate dry cow antimicrobial products had significant benefits for increasing the cure rate of pathogens, lowering the incidence of new IMIs, and minimizing the risk of clinical mastitis in the first 30 DIM.

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