OBJECTIVE To assess the association between a commercially available vaccine against Moraxella bovis and cumulative incidence of infectious bovine keratoconjunctivitis (IBK) from processing to weaning (primary objective) and body weight at weaning (secondary objective). DESIGN Randomized blinded controlled trial. ANIMALS 214 calves (≥ 2 months of age) born in the spring of 2015 at an Iowa State University cow-calf research unit with no visible lesions or scars on either eye. PROCEDURES Calves were randomly allocated to receive SC administration of a single dose of a commercial vaccine against M bovis (112 enrolled and 110 analyzed) or saline (0.9% NaCl) solution (111 enrolled and 104 analyzed). Calves were monitored for signs of IBK from treatment to weaning, and body weight at weaning was recorded. People involved in calf enrollment and outcome assessment were blinded to treatment group assignment. Cumulative incidence of IBK and weaning weight were compared between vaccinated and unvaccinated calves; the effect measure was the risk ratio and mean difference, respectively. RESULTS IBK was detected in 65 (59.1%) vaccinated calves and 62 (59.6%) unvaccinated calves (unadjusted risk ratio, 0.99; 95% confidence interval, 0.79 to 1.24) during the study period. No significant difference in weaning weights was identified between vaccinated and unvaccinated calves (unadjusted effect size, 4.40 kg [9.68 lb]; 95% confidence interval, -3.46 to 12.25 kg [-7.61 to 26.95 lb]). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the commercially available M bovis vaccine was not effective in reducing the cumulative incidence of IBK or increasing weaning weight in beef calves.