Objectives <p>This study evaluated the clinical utility of the Patient-Reported Outcomes Measurement Information System (PROMIS^®) by comparing it with objective clinical data and validated health-related quality of life (HRQOL) measures in pediatric Crohn’s disease (CD) patients.</p> Study design <p>Cross-sectional study. Pediatric CD patients (aged 8–17 years) were enrolled prospectively over eight months from an outpatient pediatric gastroenterology center. We assessed the associations between PROMIS^® Pediatric short-form measures, demographic and disease-related data, global clinical assessments, and HRQOL measures. A subanalysis according to the PCDAI (remission versus active disease) was also conducted.</p> Results <p>Thirty-one patients (mean age: 15.3; 58% female) with a mean disease duration of 2.7 years were included; 80.6% were in remission or had mild disease. The PROMIS^® score was significantly correlated with several factors: age was negatively correlated with the PROMIS^® Global Health Scale (<i>r</i>=-0.399; <i>p</i> = 0.026) and Life Satisfaction (<i>r</i>=-0.359; <i>p</i> = 0.047); sex was associated with the PROMIS^® Cognitive Function Scale (t = 2.20; <i>p</i> = 0.038), favoring males; and school level was inversely related to the PROMIS^® Peer Relationships (F = 3.90; <i>p</i> = 0.003). Clinical assessments also revealed significant correlations between hemoglobin and PROMIS^® Global Health (<i>r</i> = 0.356; <i>p</i> = 0.049) and pain interference (<i>r</i>=-0.360; <i>p</i> = 0.046) and between ferritin and PROMIS^® Meaning and Purpose (<i>r</i> = 0.435; <i>p</i> = 0.016) and cognitive function (<i>r</i> = 0.450; <i>p</i> = 0.011). Disease activity assessments correlated significantly with multiple PROMIS^® measures, with better scores in patients in remission. Treatment changes, particularly corticosteroid treatment, negatively impacted the PROMIS^® Anxiety and Life Satisfaction scores. IMPACT-III scores correlated positively with PROMIS^® Global Health, Meaning and Purpose, Life Satisfaction, and peer relationships scores and negatively with Depression, Anxiety, Pain interference, and Fatigue scores. Group analysis indicated better PROMIS^® scores and HRQOL scores in remission than in active disease remission.</p> Conclusion <p>Consistent with recent evidence, PROMIS^® scores reliably reflect disease activity and HRQOL. The meaningful associations with clinical assessment and treatment efficacy reinforce the clinical relevance and utility of PROs in the patient-centered management of pediatric IBD and highlight the importance of self-reports as a gold standard tool for assessing health status.</p>