Angus Hereford calves (n = 159; 87 heifers and 72 steers) were ranked by sex, body weight (BW), and age, and assigned to 1 of 3 vaccination schemes against the bovine respiratory disease (BRD) complex: 1) vaccination at weaning (d 0) and booster at feedyard entry (d 30; CON, n = 53), 2) vaccination 15 d before weaning (d -15) and booster 15 d before feedyard entry (d 15; EARLY, n = 53), and 3) vaccination 15 d after weaning (d 15) and booster 15 d after feedyard entry (d 45; DELAYED, n = 53). Calves were maintained on pasture from d -15 to 30, transported (d 30) for 480 km to a commercial growing yard, and moved (d 180) to an adjacent finishing lot where they remained until slaughter (d 306). Calves were assessed for BRD signs daily from d 0 to 306 according to the DART system. Blood samples were collected and BW recorded on d -15, 0, 15, 30, 45, 60, 75, and 180. Hot carcass weight was recorded upon slaughter, and carcass quality assessed after a 24-h chill. No treatment effects were detected (P 0.49) for BW gain and carcass traits (P 0.32). Incidence of BRD (d 0 to 306) was lessened (P < 0.01) in EARLY vs. CON and DELAYED, and similar (P = 0.17) between CON and DELAYED. Treatment day interactions were detected (P 0.02) for serum antibody titers against bovine herpesvirus-1, bovine viral diarrhea virus-1, parainfluenza3, and bovine respiratory syncytial virus, which were greater (P 0.05) in EARLY vs. CON and DELAYED upon feedyard entry. Hence, anticipating initial and booster vaccination against respiratory pathogens to provide both doses prior to shipping appears to be a valid strategy to enhance cattle health responses and mitigate BRD in feedyards.