Tritrichomonas foetus is a sexually transmitted reproductive pathogen of cattle that causes transient infertility, early embryonic death, metritis, pyometra, and sporadic abortions. The objective of this research was to assess the impact on reproductive health of vaccinating naïve heifers with a killed T. foetus vaccine (TrichGuard) before experimental exposure followed by breeding. A total of 40 beef heifers were randomly assigned into two treatment groups. Heifers where then vaccinated with two doses of TrichGuard or sham vaccinated with 0.9% sterile saline according to their respective groups. Sixty days following vaccination or sham vaccination, heifers were intravaginally inoculated with 2 × 106 organisms of a cloned isolate of T. foetus of bovine origin (CDTf-4) during synchronized estrus. Three days following inoculation of T. foetus, bulls free of T. foetus were introduced for natural breeding. Three bulls were maintained with the 40 heifers (20 vaccinated; 20 sham vaccinated) for a 49-day breeding season. Cervical mucous samples were obtained from each heifer at Day 0 and at 29 additional time points throughout the study for T. foetus culture. Pregnancy assessments were performed routinely by using transrectal palpation and ultrasonography. Pregnancies were detected in 19/20 (95%) vaccinated heifers and 14/20 (70%) sham-vaccinated heifers (P = 0.046). Only 4/20 (20%) of the sham-vaccinated heifers gave birth to a live calf compared with 10/20 (50%) of the vaccinated heifers (P = 0.048). Thus, embryonic or fetal loss was detected in 9/19 (47%) vaccinated heifers and 10/14 (71%) sham-vaccinated heifers (P = 0.153). The interval of time between inoculations with T. foetus and conceptions of pregnancies that were maintained until birth did not differ significantly between groups (vaccinated = 18.7 days; sham-vaccinated = 17.3 days; P = 0.716). The infectious challenge in this study proved to be very rigorous as a positive culture was detected from all heifers. The culture-positive results on the last culture day did not differ significantly (P = 0.115) between vaccinated heifers (63.9 days) and sham-vaccinated heifers (79.2 days). All uterine culture samples collected from the 26 nonpregnant heifers on Day 207 postinoculation did not result in the detection of T. foetus. These findings indicate that the killed, whole cell vaccine used in this study (TrichGuard) was effective in improving reproductive health evidenced by significantly reducing losses associated with T. foetus infections.