Objective: To determine if adjuvants differ in their ability to trigger lesions associated with porcine circovirus type 2 (PCV2). Methods: Ninety pigs randomly assigned to five groups were vaccinated intramuscularly at 4 and 6 weeks of age with 2 mL of a commercial Mycoplasma hyopneumoniae (M hyo) vaccine with oil-in-water adjuvant (Group 1), a commercial M hyo vaccine with an aqueous-carbopol adjuvant (Group 2), an experimentally produced M hyo vaccine with an oil-in-water adjuvant (Group 3), or an experimentally produced M hyo vaccine with an aluminum hydroxide adjuvant (Group 4), or were sham-vaccinated with saline (Group 5). All pigs were inoculated intranasally at 6 weeks of age with PCV2 (Day 0). Half of the pigs were necropsied at Day 21 and the remaining pigs at Day 35. Results: No clinical disease was observed in any pigs during this study. At Day 21, lymphoid depletion was more severe in all M hyo-vaccinated pigs than in the saline-treated pigs (P < .05). At Day 35, greater amounts of PCV2 DNA were found in serum, more severe lymphoid lesions were observed, and more PCV2 antigen was detected in lymphoid tissues in Groups 1 and 3 (oil-in-water adjuvant) compared to Groups 2, 4, and 5 (P < .05). Implications: Under the conditions of this study, oil-in-water adjuvanted vaccines are more likely to enhance PCV2-associated lesions than aqueous-carbopol or aluminium hydroxide adjuvanted vaccines. Practitioners must weigh benefits and efficacy of vaccines intended to control coinfections against the potential negative effect certain vaccines may have oil PCV2 replication.