Background/objectives Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. Subjects/methods A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17-56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. Results Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35-1168) mm(3) vs. 879 (775-1086) mm(3); P amp;lt; 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (r(s) = -0.67; P amp;lt; .001; r(s) = -0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm(3) increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5-3.9; P amp;lt; 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. Conclusions A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.