Growth hormone deficiency (GHD) is associated with truncal obesity. We aimed at identifying factors that determine the body mass index (BMI) of untreated GHD children and the changes in BMI during 2 years of GH therapy in 348 Dutch GHD children registered in the National GH Registration Database. BMI was expressed as a standard deviation score (SDS). Before GH therapy, the mean (95% CI) BMI-SDS in all GHD children (0.09 (-0.05 to 0.24) SDS) was comparable to normal children. Patients with GHD due to a cranial tumour have a higher BMI (1.03 (0.69-1.36) SDS; p < 0.0001) as well as those with multiple pituitary hormone deficiencies (0.35 (0.14-0.57) SDS; p = 0.005) and patients who are in puberty at start of GH therapy (0.60 (0.13-1.08) SDS; p = 0.036). During GH therapy BMI initially decreased to reach a nadir of -0.28 (-0.35 to -0.21) SDS at 6 months. Thereafter BMI progressively increased to -0.09 (-0.18 to -0.04) SDS after 24 months. A higher initial BMI-SDS resulted in a larger decrease in BMI-SDS. We showed that this can be sufficiently explained by a regression to the mean effect.