Metritis is one of most prevalent and economic detrimental postpartum health disorders in dairy cows. However, there is lack of controlled prospective cohort studies evaluating its economic impact for dairy cows. The objective of this study was to perform an economic comparison of metritic treated cows using data from a previous prospective controlled cohort study that compared the efficacy of ampicillin trihydrate and ceftiofur hydrochloride. We hypothesized that an economic analysis considering differences in costs of antibiotics, labor, and feed, mean time to pregnancy, and milk production would determine the least costly treatment strategy for metritis. Cows diagnosed with metritis were blocked by parity and within each block allocated randomly to receive either ampicillin (n = 259), or ceftiofur (n = 269). A control group of cows without metritis matching parity and days in milk was also enrolled (n = 268) to be used as a baseline for comparison. Data on cows sold or dead, days open, and milk production (305 d) were used along with drug and commodity prices to create a per case cost of metritis. Mean time to pregnancy was analyzed using PROC PHREG and LIFETEST on SAS 9.4. Percent of dead or sold, feeding cost, milk production, and final cost analysis (with and without the value of feeding withdrawal milk to calves) were performed using PROC GLIMMIX. Cows without metritis had reduced mean time to pregnancy, reduced feeding cost, and increased milk production (P < 0.01) than counterpart diagnosed with metritis and these differences were accounted in the final cost analyses. There were no differences among treatments for mean time to pregnancy, percent of sold or dead, and feed costs (P > 0.05). Milk production tended to be greater (P = 0.07) in cows treated with for ampicillin (9,078 kg) than cows treated with ceftiofur (8,732 kg). The final cost per case for treating metritis was higher (P < 0.001) for cows treated with ceftiofur ($387.63) than for ampicillin, either feeding milk from withdrawal period to calves ($294.83) or not ($328.70), indicating that ampicillin was the least costly treatment for metritis.