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The objective of this study was to compare two strategies for screening and subsequent treatment of acute puerperal metritis (APM) in dairy cows. Therefore, we conducted a study on 79 cows with APM (cows with an enlarged uterus with fetid watery red-brown vaginal discharge and fever >39.5 °C) and 114 healthy control cows. Cows with APM were divided into two groups (treated, N = 67 cows; not treated, N = 12 cows). The treated animals were further subdivided into two groups (treated between Day 1 and 4 post partum, N =12 and treated between Day 5 and 10, N = 55). Serum haptoglobin concentrations, milk yield, cure rate, prevalence of endometritis, and cervical diameter on days in milk (DIM) 21 to 27 were compared between the groups. Cows were defined as cured when their rectal temperature was <39.5 °C 4 days after treatment and fever did not rebound over 39.4 °C until the end of the screening period which was DIM 10. The results of this study did not show any significant differences in cure rates, milk yield, or serum haptoglobin concentrations on DIM 2, 5, and 10 and subsequent uterine health (DIM 21-27). Considering this study as a proof of concept study, we conclude that there might not be a negative effect after a screening and treatment protocol beginning at DIM 5 and leaving early APM cows untreated. This hypothesis needs to be confirmed by a larger field study. Furthermore, antimicrobial therapy could be avoided in 12 of 55 cows (21.8%) in group 2 because of the protocol implementing treatments after DIM 5. These cows did not show signs of APM during the following 5 days. Therefore, these animals were considered as self-recovered leading to a cure rate of at least 21.8% (12 of 55 cows).