We applied item response theory based person-fit analysis (PFA) to data of the Outcome Questionnaire-45 (OQ-45) to investigate the prevalence and causes of aberrant responding in a sample of Dutch clinical outpatients. The Formula person-fit statistic was used to detect misfitting item-score patterns and the standardized residual statistic for identifying the source of the misfit in the item-score patterns identified as misfitting. Logistic regression analysis was used to predict person misfit from clinical diagnosis, OQ-45 total score, and Global Assessment of Functioning code. The Formula statistic classified 12.6% of the item-score patterns as misfitting. Person misfit was positively related to the severity of psychological distress. Furthermore, patients with psychotic disorders, somatoform disorders, or substance-related disorders more likely showed misfit than the baseline group of patients with mood and anxiety disorders. The results suggest that general outcome measures such as the OQ-45 are not equally appropriate for patients with different disorders. Our study emphasizes the importance of person-misfit detection in clinical practice.