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The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Our objectives were to compare the efficacy of ketoprofen or ceftiofur for treatment of metritis in dairy cows considering subsequent health, production, and reproduction. Cows from 2 commercial dairy farms in Ontario, Canada were examined with a Metricheck device 3 times per week from 2 to 14 DIM. Cows with metritis (fetid vaginal discharge; n = 193) were blocked by parity and fever (rectal temperature ≥39.5°C or <39.5°C) and within each block per farm, randomly assigned to receive 3 mg/kg BW of ketoprofen (KET) or 2.2 mg/kg of ceftiofur hydrochloride (CEF), once a day for 3 d. Day of enrollment was considered study d 0. Rectal temperature and attitude were evaluated in cows with metritis on study d 0, 3, 4, 7, 10, and 13, and vaginal discharge was evaluated on study d 4, 7, 10, and 13. Body condition was scored at enrollment and at 35 DIM, and serum concentration of haptoglobin was measured at d 0, 2, 4, and 7. Cows with rectal temperature ≥39.5°C or a depressed attitude on d 3 were classified as clinical failure and received treatment with ceftiofur for 3 d (KET), or 2 additional days (CEF), to a maximum of 5 d of treatment with ceftiofur. At 35 ± 3 DIM cows were examined for uterine involution via transrectal palpation, purulent vaginal discharge (PVD) via Metricheck, and endometritis via endometrial cytology. Time to onset of cyclicity was assessed by serum progesterone (P4) measurements at 28, 42, and 56 DIM. Contemporary cows from the same farms without metritis (NOMET; n = 1,043) were used for comparison. Data were analyzed with mixed linear or logistic regression or Cox's proportional hazard models, including herd as a random effect. The proportion of clinical resolution of metritis on d 3 (96% vs. 92%), of cows with fever (from d 3 to d 13 after enrollment) or fetid discharge (from d 4 to d 13 after enrollment), and the number of medical treatments (3.1 vs. 3.3) were not different between CEF and KET, respectively. Cows in KET received fewer antibiotic treatments than cows in CEF (0.3 vs. 3.1). Uterine involution, prevalence of PVD (50% vs. 47%) and subclinical endometritis (6.6% vs. 4.3%), and proportion of cyclic cows (82% vs. 86%) did not differ between CEF and KET. Cows in KET had greater serum haptoglobin concentration from d 2 to 7 after enrollment. The incidence of mastitis, lameness, or displaced abomasum to 60 DIM and subclinical ketosis to 21 DIM did not differ among CEF, KET, and NOMET. There were no differences in median time to first AI (CEF = 68 d, 95% CI: 65–70; KET = 69 d, 95% CI: 68–72; NOMET = 69 d, 95% CI: 68–70), median time to pregnancy (CEF = 118 d, 95% CI: 92–145; KET = 113 d, 95% CI: 90–135; NOMET = 105 d, 95% CI: 101–109), pregnancy at first AI at 33 d after insemination (CEF = 42%; KET = 41%; NOMET = 41%), pregnancy loss after first AI (CEF = 8%; KET = 11%; NOMET = 8%), hazard of pregnancy, or hazard of culling up to 300 DIM. Milk yield was not different between CEF and KET during the first 10 wk, but was lesser in KET at wk 2 and 4 and CEF at wk 2, 4, and 6 than in NOMET. In this pilot-scale study, given early detection, we did not detect differences in subsequent health, milk yield, or reproductive performance in cows with metritis initially treated for 3 d with CEF or KET. Additional, larger studies are warranted. [ABSTRACT FROM AUTHOR]