The aim of this study was to evaluate the effect of 24 months of growth hormone (GH) replacement on glucose metabolism and visceral fat in 17 adults with GH deficiency: 9 men and 8 women; age 40 +/- 1.8 yr. [range 20-61] and body mass index 25 +/- 0.8 Kg/m2. Glucose metabolism was evaluated by a standard oral glucose tolerance test (OGTT), by the homeostatic model assessment (HOMA) insulin resistance index and by the insulin sensitivity index (ISI)-composite derived from the OGTT. Visceral fat was evaluated by CT scan.Twenty-four months of GH replacement induced an increase in the prevalence of abnormal glucose tolerance, with significant progressive increment in 2h-OGTT insulin levels at 3, 12 and 24 months (p = 0.005). Plasma glucose levels and ISI-composite did not alter during the study. HOMA-IR index increased only in the group of patients (n = 8) who had abnormal OGTT at 24 months (p = 0.012). Visceral fat reduced at month 12 and remained decreased until the end of the study (p = 0.009). In conclusion, the present study suggests that adults with GH deficiency after twenty-four months of GH replacement developed abnormal glucose tolerance, probably due to an increase in insulin resistance, associated with higher insulin levels, despite favorable alterations in body composition.