The objective of this study was to compare the protection against challenge with porcine circovirus 2 (PCV2) induced by an experimental vaccine based on open reading frame (ORF) 2 of PCV2 DNA plus an adjuvant (aluminum hydroxide, cobalt oxide, or liposome) and a commercial PCV2 subunit vaccine. A total of 35 colostrum-fed, cross-bred, conventional piglets were randomly divided into 7 groups. The commercial vaccine was more efficacious against PCV2 challenge than the 4 experimental vaccines according to immunologic, virologic, and pathological outcomes. The pigs inoculated with the experimental vaccine containing the liposome adjuvant had significantly higher levels ( < 0.05) of neutralizing antibodies and interferon-γ-secreting cells, and significantly lower levels ( < 0.05) of PCV2 viremia than the pigs inoculated with the other experimental vaccines. The pigs inoculated with the experimental vaccines containing either the liposome adjuvant or the cobalt oxide adjuvant had significantly lower lymphoid lesion scores ( < 0.05) than the pigs in the group inoculated with the PCV2 DNA vaccine dissolved in phosphate-buffered saline. Liposome proved to be a potent adjuvant that efficiently enhanced both humoral and cellular immune responses induced by the PCV2 DNA vaccine.