Feline herpesvirus 1 (FHV-1)–infected cats can develop severe respiratory and ocular disease that may lead to death or euthanasia. In the United States, there are 3 vaccine formulations for prophylaxis: modified live (ML) vaccine for SC administration, ML for IN administration, and an inactivated vaccine for SC administration. In this study, 2 different vaccination strategies were compared with an unvaccinated control. In group 1 (n = 8), kittens received a single SC dose and a single IN dose of a ML vaccine concurrently. Group 2 kittens (n = 8) received a single SC dose of the same ML vaccine used in group 1. Seven days after vaccination, the 2 treatment groups and untreated control were challenged with an FHV-1 strain, and clinical scores were recorded for the next 21 days. Kittens in group 1 had significantly less severe clinical illness than those in group 2. In addition, there was significantly less FHV-1 shedding detected on DNA pharyngeal swabs in group 1 compared with group 2.