OBJECTIVES: To investigate the clinical significance of change in QoL-AGHDA score after 1 year of growth hormone (GH) replacement. METHODS: Observational data were obtained from KIMS (Pfizer International Metabolic Database).  Minimal important differences (MID) for the QoL-AGHDA score and its five domains (memory and concentration, tenseness, tiredness, self-confidence, and social isolation) were calculated using an anchor-based approach with a rating of patient-perceived treatment benefit and patient-reported change in need for assistance. Perception of treatment benefit was measured using the KIMS Patient Life Situation Form (PLSF), a 5-point ordinal assessment of change (much improved, a little improved, no change, a little worse, much worse). The effect of baseline (BL) scores on MID was analysed using the QoL-AGHDA thresholds included in the New Zealand (≥16) and England (≥11) reimbursement criteria. RESULTS: Data from 1404 patients (52% female, 96% Caucasian, mean age [SD] of 45 [14] years) were included in the analysis. Mean GH dose [SD]was 0.20 [0.14] mg/day at BL and 0.32 [0.16] mg/day during Year 1. The Spearman correlation between change in QoL-AGHDA score and perception of treatment benefit was moderately positive (0.45; p <0.01). The correlation was stronger for females and for patients with more impaired (higher) BL QoL-AGHDA scores. Using the anchor-based approach with patient-perceived treatment benefit, the MID for the QoL-AGHDA score was -4.61 at Year 1. Self-confidence was most sensitive and tenseness least sensitive of the domains in predicting patient-perceived treatment benefit. Patients requiring assistance at BL and not at Year 1 experienced the largest mean improvement in QoL-AGHDA score. CONCLUSIONS: Several national reimbursement authorities currently include the QoL-AGHDA score in eligibility criteria for access to reimbursed GH replacement. This is the first study to calculate the MID for the QoL-AGHDA score. Findings indicate that change in QoL-AGHDA score is positively correlated with patient-perceived treatment benefit.