The ultimate goal of treatment for children with orthopedic problems is to improve their health-related quality of life. Because children may lack the abilities to effectively interpret and answer the questions used to assess a patient's health-related quality of life, parent proxies have been used in such pediatric cases. Unfortunately, previous studies exploring the efficacy of these parent proxies have been inconsistent. It is therefore important to determine the level of agreement between child–parent dyads and whether agreement is mediated by variables such as disease type, demographics, instrument, and the domain being assessed. The purpose of this study was to examine the degree of agreement between children and their parents' ratings in the Child Health Questionnaire (CHQ) and the Pediatric Orthopaedic Data Collection Instrument (PODCI), two instruments commonly used to assess health-related quality of life in children. The CHQ, PODCI, and standard demographic and clinical data were collected from parents and children between the ages of 5 and 18 years with a wide range of musculoskeletal problems. There was a strong level of agreement between child and parent responses for most of the domains in both instruments. Exceptions included Physical Functioning (PF), General Health (GH), and Mental Health (MH) in the CHQ, and Expectations in the PODCI. All four of these domains exhibited significant differences between the two respondent groups and had medium effect sizes. Children reported a higher level of PF and lower levels of both GH and MH than their parents. Additionally, parents reported significantly higher expectations for treatment than children did. None of the regressions yielded significant β values for child age, parent sex, match/no match between parent–child sex, and scoliosis/nonscoliosis diagnosis. These significant discrepancies were not driven by specific subsamples; therefore, we concluded that these discrepancies can be generalized to the pediatric orthopedic population. Our results also indicate that the CHQ is more sensitive than the PODCI to the rating differences between children and parents. The results of this study can serve clinicians in pediatric orthopedic surgery as a guide for not only selecting the most appropriate instruments for assessment but also for interpreting treatment outcomes most meaningfully. Level of Evidence is the Level II Prognostic Study.