Objectives of the study were to compare the effects of 2 metritis treatments on health, reproductive, and productive parameters of Holstein cows. Cows from 2 herds were examined at 4, 6, 8, 10 and 12 DIM for metritis (fetid, watery, red/brown uterine discharge). On the day of enrollment (d 0), cows were paired by parity and severity of metritis {metritis vs. puerperal metritis [rectal temperature (RT) ≥ 39.5°C]} and assigned randomly to Ampicillin (AMP) or Ceftiofur Crystalline Free Acid (CCFA) treatments. Cows enrolled in the AMP (n = 307) treatment were moved to a hospital pen where they were treated once daily for 5 d and were moved back to their original pen 72 h after the last treatment (d 7). Cows enrolled in the CCFA (n = 306) treatment remained in their original pen and received 2 doses of CCFA, 72 h apart. Contemporary healthy cows (POS = 636) were paired by parity with metritic cows and were enrolled in the study. On d 4, 6 and 11 after enrollment, cure was defined based on uterine discharge alone (no fetid, watery, red/brown uterine discharge) and uterine discharge and RT (<39.5°C). Cows were examined at 28 ± 3 DIM for purulent vaginal discharge (PVD) and at 35 ± 3 DIM for endometritis. All cows were enrolled in the Presynch-Ovsynch at 37 ± 5 DIM and pregnancy was diagnosed at 40 ± 3 and 60 ± 7 d after AI. Individual milk yield was measured monthly and weekly milk yield from calving to 14 wk postpartum are reported. Treatment did not affect cure rates on d 4 (P ≥ 0.67), 6 (P ≥ 0.37), and 11 (P ≥ 0.43), but CCFA cows had (P < 0.01) lower RT than AMP cows (102.1 ± 0.1 vs. 102.4 ± 0.1°C). Cows in the AMP treatment had higher (P = 0.05) incidence of PVD (79.3 vs. 70.7%) and tended (P = 0.06) to have higher incidence of endometritis (72 vs. 56.9%). Likelihood of pregnancy at 40 d after first AI was not (P = 0.14) affected by treatment but, at 60 d after AI, cows treated with CCFA were (P = 0.05) less likely to be pregnant (22.3 vs. 28.4%). Finally, treatment had no effect on milk (P = 0.40). In conclusion, despite slight improvements in uterine health, CCFA treatment resulted in reduced pregnancy to first AI compared with AMP treatment.