Holstein cows (n = 51) that had been diagnosed with toxic puerperal metritis were used to determine the treatment efficacy of various antibiotics. On the day of diagnosis, cows affected with toxic puerperal metritis were assigned randomly to three treatment groups. Cows in groups 1 and 2 received 22,000 IU/kg of procaine penicillin G i.m. for 5 d. In addition, cows in group 2 received an intrauterine infusion of 6g of oxytetracycline on d 1, 3, and 5. Cows in group 3 received 2.2 mg/kg of ceftiofur sodium i.m. for 5 d. Dependent variables used to determine antibiotic efficacy included milk yield on d 1 through 12, rectal temperature on d 1 through 5, and serum haptoglobin concentration on d 1, 3, and 5. No difference was observed among groups for milk yield on d 1 and 12 or for temperature on d 1 and 5. Serum haptoglobin was elevated to>10 mg/dl for cows in all groups; however, no difference was observed among groups on d 1 and 5. Because all groups showed a favorable response, this study suggests that there is no difference in treatment efficacy among antibiotics used to treat cows affected with toxic puerperal metritis.