AbstractBackgroundSickle cell disease (SCD) is an inherited chronic disease that is characterized by complications such as recurrent painful vaso‐occlusive events that require frequent hospitalizations and contribute to early mortality. The objective of the study was to report on the initial measurement properties of the new PedsQL™ SCD Module for pediatric patient self‐report ages 5–18 years and parent proxy‐report for ages 2–18 years.ProcedureThe 43‐item PedsQL™ SCD Module was completed in a multisite study by 243 pediatric patients with SCD and 313 parents. Participants also completed the PedsQL™ 4.0 Generic Core Scales and PedsQL™ Multidimensional Fatigue Scale.ResultsThe PedsQL™ SCD Module Scales evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self‐report α = 0.95; parent proxy‐report α = 0.97), and good reliability for the nine individual scales (patient self‐report α = 0.69–0.90; parent proxy‐report α = 0.83–0.97). Intercorrelations with the PedsQL™ Generic Core Scales and PedsQL™ Multidimensional Fatigue Scales were medium (0.30) to large (0.50) range, supporting construct validity. PedsQL™ SCD Module Scale Scores were generally worse for patients with severe versus mild disease. Confirmatory factor analysis demonstrated an acceptable to excellent model fit.ConclusionsThe PedsQL™ SCD Module demonstrated acceptable measurement properties. The PedsQL™ SCD Module may be utilized in the evaluation of SCD‐specific health‐related quality of life in clinical research and practice. In conjunction with the PedsQL™ Generic Core Scales and the PedsQL™ Multidimensional Fatigue Scale, the PedsQL™ SCD Module will facilitate the understanding of the health and well‐being of children with SCD. Pediatr Blood Cancer 2013;60:1338–1344. © 2013 Wiley Periodicals, Inc.