OBJECTIVES: To quantify the differences in health-related quality of life within and between adults with GHD and the general population in Spain and England & Wales (E&W), respectively, using the disease-specific instrument QoL - Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA ). METHODS: QoL-AGHDA is a 25-item questionnaire that elicits yes/no responses to personal statements describing problems that characterize aspects of HrQoL in growth hormone deficiency. A high QoL-AGHDA score denotes poor HrQoL. The Spanish population sample comprised 940 individuals, and the England and Wales sample 921. These survey data were collected in studies reported elsewhere (Badia and Koltowska–Häggström, respectively). Patient data were retrieved from KIMS (Pfizer International Metabolic Database). The number of patients from the two countries were 315 and 836, respectively. Student t-tests were performed on mean data for groups formed by 10-year age bands and gender. RESULTS: For Spain the mean QoL-AGHDA was 11.0 for patients and 5.1 in the general population. For E&W the corresponding means were 14.7 and 6.7. The mean deficits for patients compared with the general population were similar in all age- and gender groups and were statistically significant (p<0.0001). The mean patient QoL-AGHDA from E&W were significantly higher in most age and gender categories compared with the Spanish patients (p<0.05). The general population QoL-AGHDA scores in men did not differ significantly between countries (Spain = 5.9 vs. E&W=6.2), but women from Spain scored significantly lower (higher HrQoL) than women from E&W (3.9 vs. 7.0; p<0.0001). CONCLUSIONS: This study confirms the extent of deficit in HrQoL in adults with GHD compared to general population. For patient comparisons, caution is needed in interpreting these results, since the eligibility criteria for GH replacement differ between the two countries. The reasons for gender variability between Spain and E&W general population requires further studies.