The objective of this study was to evaluate the efficacy and economic efficiency of a systemic treatment of toxic puerperal metritis in dairy cows with ceftiofur. Cows with abnormal vaginal discharge at a postpartum examination (d 4 to 6 after calving) and a rectal temperature > or = 39.5 degrees C were assigned to three treatment groups. Cows in group 1 (n = 70) received 600 mg of ceftiofur intramuscularly (i.m.) on 3 consecutive days. Cows in group 2 (n = 79) received an intrauterine treatment with antibiotic pills consisting of 2500 mg of ampicillin and 2500 mg of cloxacillin and an additional 6000 mg (i.m.) of ampicillin. This treatment was performed on 3 consecutive days. Cows in group 3 (n = 78) received the same intrauterine treatment as in group 2. In addition, 600 mg of ceftiofur was administered i.m. on 3 consecutive days. Body temperature was recorded daily for 6 d after first treatment. There were no significant differences among the groups regarding clinical efficacy at d 6 after first treatment. The cure rates based on rectal temperatures declining to below 39.5 degrees C on d 6 after treatment were 82.9, 84.8, and 84.6% for groups 1, 2, and 3, respectively. Reproductive performance did not differ significantly between group 1 and groups 2 and 3 for any of the measures tested. A financial analysis with 87 different cost scenarios demonstrated that a systemic treatment of toxic puerperal metritis in cattle with ceftiofur is an effective alternative to the combination of local and systemic treatments.