OBJECTIVES: The goal of treating acromegaly is directed at removing the tumor, preventing tumor re-growth and reducing long-term morbidity and mortality. For this purpose, different health resources are necessary. This study evaluates the disease resources and costs in Spain. METHODS: An epidemiological, prospective, naturalistic, multicentric study (30 endocrinologists) involving acromegalic patients with micro (≤10mm) or macro (>10mm) adenomas was performed. Patients were categorised as Surgical Group (SG) (surgery in the 6 months before inclusion or during follow-up period and somatostatin analogue (SA) treatment for <6 months during the pre-surgery period) and Medical Treatment Group (MTG) (patients receiving SA treatment for ≥6 months, with/without surgery following SA treatment). Resource data were collected from standard visits during a 2-years period. RESULTS: The study included 74 patients (56 SG and 18 MTG). Most patients were women (62%). The mean (SD) age was 49 (14) years. The annual direct acromegaly cost per patient is €9,668 (€9,223 SG vs. €11,054 MTG). The cost of illness was higher in patients with macroadenoma than in microadenoma (€11,053 vs. €5,809), and it is increased in young patients (<40 years). Surgical procedures in acromegaly (involving hospitalization and complementary tests) constitute the 22% and 8% of the illness cost in SG and MTG patients. Additionally, hospitalizations in intensive care units (50% SG vs. 22% MTG patients), emergency visits (21% SG vs. 6% MTG) and the presence of adenoma complications (73% SG vs. 44% MTG) constitute a source of cost increment in these patients. Patients who accomplish with the most strict study clinical control criteria (GH<1.0 and IGF-1<100%) showed the lowest direct cost of illness (€6,169 vs €12,990). CONCLUSIONS: The economic cost of acromegaly is dependent on the clinical control of the disease. Direct cost of illness is the half that the cost in non controlled patients.