OBJECTIVE: To assess responsiveness and reproducibility using the estimates of test-retest reliability for the Quality of Life Inventory-Disability (QI-Disability), accounting for changes in child health and parental stress. METHOD: Quality of Life Inventory-Disability was administered twice over a 1-month period to a sample of 55 primary caregivers of children (aged 5-19 years) with intellectual disability. Caregivers also reported their child's physical and mental health and completed a 4-item Perceived Stress Scale to assess parental stress. Fixed-effects linear regression models examined responsiveness of QI-Disability to the reported change in child health and parental stress. Reliability was then assessed using intraclass correlations (ICCs) calculated from QI-Disability scores adjusted for changes in child health and parental stress. RESULTS: Five of 7 unadjusted ICC values indicated at least moderate agreement (>0.70), and 2 values indicated fair agreement. After accounting for changes in child health and parental stress, adjusted ICC values showed substantial agreement for the total QI-Disability score and 4 domain scores (adjusted ICC ≥ 0.80). Adjusted ICC scores indicated moderate agreement for the Physical Health domain (adjusted ICC = 0.68) and fair agreement for the Positive Emotions domain (adjusted ICC = 0.58). Improvements in a child's physical health rating were associated with higher total, Physical Health, and Positive Emotion domain scores, whereas improvements in mental health were associated with higher total and Negative Emotions domain scores, indicating better quality of life. Changes in parental stress did not have a statistically significant relationship with quality of life. CONCLUSION: Satisfactory test-retest reliability was shown. Preliminary evidence indicates that QI-Disability is responsive to changes in child health, but not to differing levels of parental stress.