A case-control study was conducted to assess the association of major swine viral pathogens, including porcine circovirus type 2 (PCV2) with postweaning multisystemic wasting syndrome (PMWS). Cases were defined as individual pigs with a clinical history of progressive weight loss and respiratory signs and that were subsequently diagnosed with PMWS on the basis of characteristic histopathological lesions. Controls were pigs clinically unaffected and/or from herds in which PMWS had not been diagnosed and with no clinical signs compatible with PMWS. A total of 31 cases and 56 controls were identified from diagnostic submissions or farms within a 6-month period. Among viruses examined, PCV2 appeared to be the most strongly associated with PMWS (P<.05). Risk for PWMS was much higher if animal was coinfected with porcine reproductive and respiratory syndrome virus (odd ratio =31.2). However, PCV2 was found in 62.5% of the control animals and was not detected in 2 of the 31 PMWS pigs. Furthermore, no significant genetic difference was observed among PCV2 isolates from PMWS and clinically normal pigs. The role of PCV2 in PMWS remains to be reassessed.