OBJECTIVES: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder. There are four etiologies of AS, with maternal chromosome 15q11q13 deletion accounting for most cases. This study describes healthcare resource use (HRU) and medical service use (MSU) among patients with AS and compares use by molecular subtype. METHODS: The AS Natural History study (NHS) is a longitudinal observational study on the development, behavior, and medical problems of individuals with AS. Caregiver-reported information collected at the baseline visit was used to assess HRU and MSU. HRU measures included hospitalization, surgery, and medication use. MSU included early childhood intervention (EI), physical therapy (PT), occupational therapy (OT), and speech therapy (ST).   RESULTS: Data were available on 302 patients. Mean age at baseline visit was 6.0+5.9 years (range: 0.4 to 40.6) and 70% had deletion subtype. Sixty-eight percent of patients had at least one hospitalization; average number of hospitalizations was 2.3 (95% CI: 2.1-2.5) and average length of stay was 4.5 days (95% CI: 3.8-5.2). Most common reasons for hospitalization were seizures (40%), lower respiratory infection (21%), and surgery (11%). Fifty-seven percent of patients had at least one surgery, for insertion of ear tubes (34%), strabismus (30%), tonsillectomy and adenoidectomy (25%), and G-tube/fundoplication (8%). The most frequently prescribed medications were anticonvulsants (clonazepam (24%), levetiracetam (22%), valproic acid (22%), and topiramate (16%)) and gastro-esophageal reflux disease medications (ranitidine (24%) and lansoprazole (19%)). Non-prescription medication use included melatonin (42%) and various supplements (34%). Resource use was high, with participants receiving EI (95%), PT (90%), OT (88%) and ST (86%). HRU and MSU were similar when comparing patients with deletions to those with other molecular subtypes. CONCLUSIONS: This is the first study to evaluate HRU and MSU among AS patients. Results show high hospitalization rate and high MSU; use does not vary with molecular subtype.