An exploratory case-control study was carried out in Spain in 2002/2003, involving 62 pig farms of different production systems to assess risk factors that, in association with PCV2 infection, induce postweaning multisystemic wasting syndrome (PMWS) expression. To achieve this objective two groups of farms selected according to their PMWS status were compared: "cases" (farms with clinical PMWS, n = 32) and "controls" (farms without clinical PMWS, n = 30). A filled-in questionnaire and 45 blood samples (15 sows, and two groups of 15 pigs of 12 and 20 weeks of age, respectively) were obtained from each farm. Additionally, two to three diseased pigs were necropsied and relevant tissues to diagnose PMWS collected when PMWS was clinically suspected ("case" farms). A statistical analysis to compare "case" versus "control" farms was performed with the variables obtained from the questionnaire (191 variables) and the serologic test results (20 variables). Data were analysed using conditional logistic regression with a nested n:m matched design taking into account the farm size. Three variables were found significant in the final model: two related to vaccination scheme and one to PCV2 seroprevalence in growing pigs. Vaccination of gilts against PRRSV increased the odds of PMWS expression and vaccination of sows against atrophic rhinitis was related to decreased odds of the disease; however, the possibility that those two factors could be spurious effects (due to the small sample size) or confounding variables cannot be ruled out. On the other hand, a higher prevalence of antibodies to PCV2 at 12 weeks of age was observed in pigs from "case" farms than in pigs from "control" farms. This result suggests that an earlier infection with PCV2 might be a risk factor for PMWS expression.