The objectives of this field study were to validate diagnostic criteria for clinical endometritis in postpartum dairy cows, to measure its impact on reproductive performance, and to compare the effect of treatment with intrauterine (i.u.) antibiotic or intramuscular (i.m.) prostaglandin F-2alpha (PGF(2alpha)) on time to pregnancy. Data were collected from 1865 cows in 27 herds, including history of dystocia, twins, retained placenta, or metritis. All cows were examined once between 20 and 33 days in milk (DIM) including external inspection, vaginoscopy, and trans-rectal palpation of the cervix, uterus and ovaries. All cows were followed for a minimum of seven months until pregnancy or culling. Survival analysis was used to derive a case definition of endometritis based on factors associated with increased time to pregnancy. The significance of clinical findings depended on the interval postpartum when examination took place. The presence of purulent uterine discharge or cervical diameter greater than 7.5 cm after 20 DIM, or mucopurulent discharge after 26 DIM identified cows with clinical endometritis. Given vaginoscopy, no diagnostic criteria based on palpation of the uterus had predictive value for time to pregnancy. The prevalence of clinical endometritis was 17%. Vaginoscopy was required to identify 44% of these cases. Accounting for parity, herd, and ovarian status, cows with clinical endometritis took 27% longer to become pregnant (hazard ratio (HR)= 0.73), and were 1.7 times more likely to be culled for reproductive failure than cows without endometritis. There were 316 cows with endometritis assigned randomly to receive 500 mug cephapirin benzathine i.u., 500 mug cloprostenol i.m., or no treatment. The rate of resolution of clinical signs 14 d after treatment was 77% and was not affected by treatment. Survival analysis was used to measure the effect of treatment on time to pregnancy. There was no benefit of treatment of endometritis before 4 weeks postpartum. Administration of PGF(2alpha) between 20 and 26 DIM to cows with endometritis that did not have a palpable CL was associated with a significant reduction in pregnancy rate. Between 27 and 33 DIM, cows with endometritis treated with cephapirin i.u. had a significantly shorter time to pregnancy than untreated cows (HR = 1.63). In this time period, there was no difference in pregnancy rate between PGF(2alpha) and untreated cows, but the difference in pregnancy rate between cows treated with cephapirin i.u. and with PGF(2alpha) was not statistically significant. Treatment of postpartum endometritis should be reserved for cases diagnosed after 26 DIM, based on criteria that are associated with subsequent pregnancy rate.