Recent publications suggest PCV2 vaccine-induced protection is superior when the vaccine and challenge are closely matched. PCV2’s evolutionary rate, propensity for recombination, and genotype shifting, all provide rationale for modernizing PCV2 vaccines. One mechanism to increase a vaccine’s epitope breadth is by designing a bivalent vaccine. The objective of these studies was to evaluate efficacy of a monovalent (PCV1-2 chimera, cPCV2a or cPCV2b) and bivalent (cPCV2a–cPCV2b) vaccine in terms of homologous and heterologous efficacy. In Study A, pigs were vaccinated with cPCV2a or saline and challenged with PCV2a or PCV2b. In Study B, pigs were vaccinated with cPCV2a, cPCV2a–cPCV2b bivalent, or saline, and challenged with PCV2a. In Study C, pigs were vaccinated with cPCV2b, cPCV2a–cPCV2b bivalent, or saline, and challenged with PCV2b. In all studies vaccines and saline were administered intramuscularly to pigs at three to four weeks of age. Virulent PCV2b or PCV2a was administered to all animals approximately three weeks post-vaccination. Both mono and bivalent vaccinated groups demonstrated significantly lower viremia, percent of animals ever viremic, percent of animals with lymphoid depletion and/or histiocytic replacement, and percent of animals with PCV2 colonization of lymphoid tissues compared to saline controls. In Study A, a biologically relevant, though not significantly different, improvement in homologous versus heterologous protection was observed. In Studies B and C, biologically superior efficacy of the bivalent cPCV2a–cPCV2b vaccine compared to either monovalent vaccine was demonstrated. Taken together, cross-protection among mismatched PCV2 vaccine and challenge genotypes is not 100%; a bivalent PCV2 vaccine may provide the best opportunity to broaden coverage to circulating strains of PCV2.