We compared the efficacy of 3 commercial vaccines against swine influenza A virus (SIV) and an experimental homologous vaccine in young pigs that were subsequently challenged with a variant H3N2 SIV, A/Swine/Colorado/00294/2004, selected from a repository of serologically and genetically characterized H3N2 SIV isolates obtained from recent cases of swine respiratory disease. The experimental vaccine was prepared from the challenge virus. Four groups of 8 pigs each were vaccinated intramuscularly at both 4 and 6 wk of age with commercial or homologous vaccine. Two weeks after the 2nd vaccination, those 32 pigs and 8 nonvaccinated pigs were inoculated with the challenge virus by the deep intranasal route. Another 4 pigs served as nonvaccinated, nonchallenged controls. The serum antibody responses differed markedly between groups. After the 1st vaccination, the recipients of the homologous vaccine had hemagglutination inhibition (HI) titers of 1:640 to 1:2560 against the challenge (homologous) virus. In contrast, even after 2nd vaccination, the commercial-vaccine recipients had low titers or no detectable antibody against the challenge (heterologous) virus. After the 2nd vaccination, all the groups had high titers of antibody to the reference H3N2 virus A/Swine/Texas/4199-2/98. Vaccination reduced clinical signs and lung lesion scores; however, virus was isolated 1 to 5 d after challenge from the nasal swabs of most of the pigs vaccinated with a commercial product but from none of the pigs vaccinated with the experimental product. The efficacy of the commercial vaccines may need to be improved to provide sufficient protection against emerging H3N2 variants.