The objective of the study was to quantify the effect of administering intrauterine cephapirin in cows ≥100 DIM affected by purulent vaginal discharge (PVD) or endometritis (ENDO) on pregnancy. A randomized controlled trial was conducted in 31 conveniently selected commercial dairy herds. In these herds, cows ≥100 DIM identified as nonpregnant during regular veterinary herd health visits were enrolled and tested for PVD (Metricheck score: fleck of pus or worse) and ENDO (cytobrush combined with a leukocyte esterase test: trace leukocytes or worse). Cows could be enrolled more than once during the study period, and the unit of interest in this study was enrollment (enrollments nested within cows nested within herds). Cows that tested positive for PVD (including cows with PVD only and those with both PVD and ENDO) or ENDO only were randomly allocated to either a treatment, which received 640 mg of intrauterine cephapirin benzathine, or a negative control that received no treatment. Cows unaffected by PVD or ENDO did not receive treatment (healthy control group). Cows from the 5 study groups were reinseminated by artificial insemination (AI) 10 d after enrollment following the same standardized timed-AI protocol (Ovsynch56). We used generalized linear mixed models (logit link) accounting for clustering at the cow and herd levels to compare study groups and compute the probability of pregnancy at AI. Season, DIM, and parity were included in the final model as confounders. Data from 1,686 enrollments (from 1,423 cows) were analyzed. A total of 498 examinations (29.6%) were classified as PVD (PVD only: n = 431; PVD and ENDO: n = 67), and 506 (29.9%) were classified as ENDO. The remaining 682 enrollments (40.5%) were classified as unaffected. Based on the final model, the probability of reproductive success was 42.9% for unaffected cows, 23.2% and 25.1% for untreated cows with PVD and ENDO, respectively, and 37.1% and 37.9% for treated cows with PVD and ENDO, respectively. These results showed that cephapirin improved the reproductive odds of cows ≥100 DIM affected by PVD or ENDO.