The optimal vaccination protocol to induce immunity in kittens with maternal antibodies is unknown. The objective of this study was to determine the effects of maternally-derived antibody (MDA) on serologic responses to vaccination in kittens. Vaccination with a modified live virus (MLV) product was more effective than an inactivated (IA) product at inducing protective antibody titers (PAT) against feline panleukopenia virus (FPV). IA vaccination against feline herpesvirus-1 (FHV) and feline calicivirus (FCV) was more effective in the presence of low MDA than high MDA. Among kittens with low MDA, MLV vaccination against FCV was more effective than IA vaccination. A total of 15%, 44% and 4% of kittens had insufficient titers against FPV, FHV and FCV, respectively, at 17 weeks of age. Serologic response to vaccination of kittens varies based on vaccination type and MDA level. In most situations, MLV vaccination should be utilized and protocols continued beyond 14 weeks of age to optimize response by all kittens.