Background: Acromegaly (ACRO) is a rare, chronic growth hormone hypersecretory disorder associated with increased morbidity and mortality. Limited information is available on the utilization and costs of healthcare by patients with ACRO. Aims: To assess the impact of ACRO healthcare utilization and costs by locations of care (LoC). Methods: A US database of prescription (Rx) drug and medical claims from Jan 2010 to Apr 2019 was analyzed. Patients with an ACRO diagnosis (Dx) were identified based on claims with ICD-9/-10 codes 253.0x/E22.0. The 12-month study period followed each patient’s first ACRO Dx in the database (the index date). ACRO patients included in the study had ≥ 2 ACRO Dxs > 30 days apart, or 1 ACRO Dx plus either a pituitary adenoma Dx or a pituitary surgery or radiosurgery claim during the study period. Costs were adjusted using the medical and Rx cost Consumer Price Indexes (CPIs). Study subjects were 18–65 yr old and had continuous eligibility during the study period. Eligible ACRO patients were matched with 20 subjects who did not have ACRO. Outcomes by LoC included costs, services, and likelihood of use and were compared using separate two-part regression models (logistic followed by generalized linear) for each outcome, controlling for demographic and job-related variables, region, and Charlson comorbidity index (CCI) scores. The likelihood models only used logistic regression. Data are shown as likelihoods or mean ± standard error. Findings are significant at P < 0.05. Results: A total of 60 patients with ACRO and 1200 controls were compared. Compared with controls, patients with ACRO had a higher likelihood of using the physician’s office (100% vs 91%, P < 0.0001), inpatient (22% vs 3%, P < 0.0005), outpatient (89% vs 38%, P < 0.0001), laboratory (62% vs 31%, P < 0.0001), and “other” locations (e.g., ambulance and claims without a specific location code, 55% vs 23%, P < 0.0001). Services performed at each LoC were higher for patients with ACRO (P < 0.01, all except outpatient hospital). Total costs were higher for the ACRO cohort compared with controls ($25,770 vs $4,059, P < 0.05). Costs by LoC were consistently higher (all reported P < 0.001) for patients with ACRO compared to controls, with differences highest in the following settings: outpatient hospital/clinic ($9,611 ± $1,793 vs $1,355 ± $74), inpatient ($8,646 ± $2,388 vs $739 ± $115), physicians’ office ($4,762 ± $678 vs$1,301 ± $43), other ($2,001 ± $583 vs $367 ± $29), and laboratory ($508 ± $93 vs $66 ± $4). Neither the costs nor likelihoods of treatment in the emergency department were significantly different between cohorts. Conclusions: Compared with commercially insured people without ACRO, patients with ACRO had greater health care utilization, in all care locations, indicating a greater burden and higher costs of ACRO patients on the healthcare system.