BackgroundMucopolysaccharidosis I (MPS-I) is one of the most common types of MPS and lysosomal storage diseases, which impose considerable amount of economic burden on society. ObjectivesThe aim of this study was to examine the cost drivers in the treatment of MPS-I patients in Iran. MethodsThis is a cost-analysis study. The prevalence approach was used to evaluate costs from the healthcare payer's perspective. The number of patients found to have α-L-iduronidase deficiency was identified using the national registry database of the Ministry of Health (MOH). The direct medical costs of the patients were evaluated. Prescriptions; medical interventions; inpatient, outpatient, and diagnostic services, and also their costs were extracted from the patient's profiles in Iran Food and Drug Administration (IFDA). The prices of the medical services were taken out from Iranian medical tariff book 2014-15. Data extraction was performed from January 2017 to March 2018. ResultsSixty-six patients were registered as MPS-I in MOH databases. The average annual healthcare cost for every patient was $87 971.99, 96.9% of which was allocated to medication therapy. Therapeutic and diagnostic services costs (2.4% and 0.7% correspondingly) were ranked second and third, respectively, but with huge differences in medication cost. ConclusionsThe average annual cost of treatment for MPS-I patients is as high as 16.2 times the GDP per capita in Iran. The highest share of the cost belongs to medication. Selecting appropriate strategies for reducing the birth of a child with MPS could support allocative efficiency of the limited resources effectively.