AIMS: To quantify the effect of treating lactating dairy cows that had histories of periparturient disorders or disease with a single intrauterine infusion of 0.5 g cephapirin, 3–6 weeks prior to the start of the seasonal breeding period. METHODS: Cows (n=690) from spring-calving dairy herds (n=22) were enrolled in a prospective case-control study if they had a history of dystocia, a dead calf at calving or within 24 h of calving, retained foetal membranes (RFM), metabolic disease, twins or a vulval discharge >13 days postpartum. Cows were blocked by age, periparturient condition and calving date, and randomly assigned to be either treated with 0.5 g of cephapirin by intrauterine infusion, or left as untreated controls. Treatment occurred 24–42 days before the planned start of mating (PSM) within each herd. In addition, the reproductive tracts of 91 cows from 4 herds were examined using a vaginal speculum and rectal palpation and cervical-os discharge was scored on a scale from 0 (nil) to 3 (purulent). RESULTS: Overall, more treated cows were retained in the trial herds until pregnancy testing than control cows (p<0.05). Average 28-day submission rate was higher (93.1% vs 87.1%; p<0.05) and PSM-to-first-service interval was shorter (9 ± 1 vs 11 ± 1 days; p<0.05) in treated than control cows. The percentage of cows not pregnant at the end of the mating period was not affected by treatment overall. However, amongst cows diagnosed with RFM, a dead calf, or vulval discharge, pregnancy rates 28 and 56 days after PSM were higher for treated than control cows (p<0.05). Cows with a purulent cervical-os discharge had lower 28-day submission rates (p<0.01), lower 28-day pregnancy rates (p<0.05) and higher non-pregnant rates at the end of mating than cows with nil or mucoid cervical-os discharges. CONCLUSIONS: Intrauterine treatment with 0.5 g cephapirin improved reproductive performance of dairy cattle, especially those that had a history of RFM, a calf dead at calving or within 24 h of calving, or a vulval discharge.