The objective of this study was to evaluate the effects of intrauterine administration of 50g of ultrapure mannose or a bacteriophage cocktail and the presence of Escherichia coli and Arcanobacterium pyogenes in the uterine lumen on uterine health and reproductive performance of lactating dairy cows. The study was conducted on a commercial dairy farm located near Ithaca, New York, from May 4 to January 20, 2011, and 597 cows were enrolled. The cows were divided randomly into 3 treatment groups, and treatments were administered at 2±1 d in milk (DIM). Treatment 1 consisted of intrauterine administration of 50g of ultrapure mannose powder divided in 4 pills; treatment 2 consisted of intrauterine administration of a bacteriophage cocktail that included 4 different phages in one pill, with a dose of approximately 10⁷ plaque-forming units; and treatment 3 consisted of intrauterine administration of one empty pill (control). Intrauterine fluid swabs were collected on day of treatment and at 10±3 DIM; uterine lavage samples were collected at 35±3 DIM. Swabs and uterine lavage samples were cultured for E. coli and A. pyogenes. The intrauterine administration of mannose and bacteriophage did not affect uterine health, reproduction performance, or outcome of intrauterine secretion cultures for E. coli and A. pyogenes. Prevalence of intrauterine E. coli at 2±1 DIM and A. pyogenes at 2±1, 10±3, and 35±3 were affected by retained placenta. Additionally, prevalence of intrauterine E. coli at 10±3 and A. pyogenes at 35±3 DIM were associated with metritis, and cows that were diagnosed with clinical endometritis at 35±3 DIM had greater prevalence of intrauterine E. coli at 2±1 DIM and A. pyogenes at 35±3 DIM. Furthermore, cows positive for E. coli at 2±1 and 10±3 DIM and for A. pyogenes at 10±3 DIM had 1.63, 2.34, and 1.54 increased odds of having metritis. Cows positive for A. pyogenes at 35±3 DIM and for E. coli at 2±1 DIM had 19.8 and 2.66 higher odds of being diagnosed with clinical endometritis, respectively. Additionally, cows negative for E. coli at 2±1 DIM were 1.39 times more likely to conceive than cows positive cows for E. coli.