To achieve more targeted antibiotic use, this research paper addresses the investigation of a quarter-selective dry cow therapy (QSDCT) on 16 commercial dairy farms based solely on the pathogen species detected. Cytobacteriological analysis was performed on quarter milk samples collected 2 weeks prior to drying off and 3 to 5 days after calving. Treatment decisions were based on results before dry-off: Only quarters infected with major bacterial pathogens were treated with antibiotics. To prevent new intramammary infections (IMI), all quarters received an internal teat sealant. A total of 1,155 dry periods were evaluated. Only 8.1% of all quarters (range per farm 2.6% – 28.8%) were treated with antibiotics at dry-off and a high bacteriological cure risk of 97.1% was determined for IMI in these antibiotic-treated quarters. For IMI caused by minor pathogens a self-cure risk of 82.1% was observed. The risk of new IMI after calving was 14.6%. Results of binomial logistic regression models indicated that self-cure of IMI by minor pathogens was not related to the pathogen group, the level of quarter somatic cell count at dry-off, or the presence of at least one other quarter infected with minor pathogens in a cow. Furthermore, the risk for new IMI in uninfected quarters was not increased by the presence of at least one quarter infected with major pathogens within cow. However, 95.4% of all IMI by major pathogens after calving were due to new IMI. In conclusion, a pathogen-based QSDCT can be successfully applied on commercial dairy farms to reduce the antibiotic use, but more attention should be paid to prevent new IMI.