Background. Few studies have compared multiple health-related quality-of-life (HRQOL) instruments simultaneously for pediatric populations. This study aimed to test psychometric properties of 4 legacy pediatric HRQOL instruments: the Child Health and Illness Profile (CHIP), the KIDSCREEN-52, the KINDL, and the Pediatric Quality of Life Inventory (PedsQL). Methods. This study used data from 908 parents whose children (ages 2-19 years) were enrolled in Florida Medicaid. Parents were asked via telephone interview to complete each instrument appropriate to the age of their children. Structural, convergent/discriminant, and known-group validities were investigated. We examined structural validity using confirmatory factor analyses. We examined convergent/discriminant validity by comparing Spearman rank correlation coefficients of homogeneous (physical functioning and physical well-being) versus heterogeneous (physical and psychological functioning) domains of the instruments. We assessed known-groups validity by examining the extent to which HRQOL differed by the status of children with special health needs (CSHCN). Results. Domain scores of the 4 instruments were not normally distributed, and ceiling effects were significant in most domains. The KIDSCREEN-52 demonstrates the best structural validity, followed by the CHIP, KINDL, and PedsQL. The PedsQL and the KIDSCREEN-52 show better convergent/discriminant validity than the other instruments. Known-groups validity in discriminating CSHCN versus no needs was the best for the PedsQL, followed by the KIDSCREEN-52, the CHIP, and the KINDL. Conclusion. No one instrument was fully satisfactory in all psychometric properties. Strategies are recommended for future comparison of item content and measurement properties across different HRQOL instruments for research and clinical use. © The Author(s) 2014.