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Introduction: Adult-onset growth hormone deficiency (AGHD) is usually the la st deficiency to be substituted in hypopituitarism. In children wit h documented GH deficiency, treatment without delay is crucial for achieving opt imal effects on growth and development. In adults, it is not known whether a delay in treatment initiation influences biochemical response and the favourable physiological effects resulting from GH replacement therapy (GHRT). Methods: A total of 1085 GH-deficient adults from KIMS (Pfizer Internatio nal Metabolic Database) were included, adequately replaced with all pituitary hormones except for GH at baseline. Patients were stratified by sex and age (20–50 y ears and ≥50 years) and subsequently divided into two groups below and above the me dian duration of unsubstituted AGHD for that subgroup. The median time of unsubs tituted GHD for the total cohort was 2.53 years (P5 = 0.35, P95 = 24.42). Results: Beneficial effects of 4 years of GHRT were observed on lipids an d quality of life in all subgroups. A decrease in waist circumference was observed o nly in older (>50 years) patients. There was no difference in IGF-I SDS and in GH dose re quired to normalize IGF-I in patients with a duration of unsubstituted AGHD above o r below the median. No relevant differences were found between the groups for anthro pometric measures, cardiovascular risk factors and quality of life scores. Conclusion: In contrast to GHD in children and adolescents, no difference c ould be established in treatment response between early or late initiat ion of GHRT in AGHD in terms of required GH dose, IGF-I, metabolic health and quality of life.