Objective: We evaluated the long-term effects of growth hormone (GH) on markers of quality of life, glucose metabolism, and lipid metabolism to validate the adequacy of long-term GH replacement therapy for adult GH deficiency (AGHD). Design: Eighty-three of 100 sequentially followed patients who received GH therapy were selected for this study. Forty-nine were men aged 26 to 78 years (mean, 52 years) and 34 were women aged 20 to 78 years (mean, 56 years). The GH-releasing peptide-2 stimulation test and arginine stimulation test were used to diagnose AGHD. The adult hypopituitarism questionnaire (AHQ) and biochemical parameters such as cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, and gyrated hemoglobin (HbA1c) were determined before treatment, at 6 months of treatment, and at 1, 2, 3, 4, 5, 6, 7, and 8 years of treatment. Considering age and sex as factors potentially influencing the effect of GH therapy, the patients were divided into age groups of <60 and >= 60 years and sex groups of men and women. Repeated measured analysis of variance (ANOVA) was employed. Results: ANOVA demonstrated significant changes in mean AHQ scores during follow-up. Comparison of individual AHQ scores with baseline values revealed sequential improvements, stabilization, and decline in QOL. A significant elevation in HbA1c level was demonstrated. LDL-C and HDL-C levels changed significantly upon GH treatment regardless of sex or age. Levels of glucose, TC or TG did not change significantly. Conclusion: The effect of GH therapy on QOL showed sequential improvements and stabilization until 6-year follow-up.