OBJECTIVES: Although aromatase inhibitors (AIs) have been shown to be more effective than tamoxifen (TMX) in delaying disease progression, reducing risk of recurrence, and improving survival among post-menopausal women with a history of breast cancer, both classes of drugs are recommended options for adjuvant endocrine therapy. We aimed to compare healthcare utilization and expenditures between the two drug classes. METHODS: This retrospective study utilized 2010-2014 data from the Medical Expenditure Panel Survey and included women aged ≥55 years with a history of breast cancer who were treated with an AI or TMX within the past 5 years. Health care utilization and annual expenditures were compared between cohorts using linear and log-transformed regression. RESULTS: The cohorts contributed 221 patient-years (Weighted N = 2,610,777) with 182 (Weighted N=2,099,698) for AIs and 39 (Weighted N = 511,079) for TMX. In the unadjusted analysis, there was no statistical difference between both groups in overall annual expenditure ($16,030 (Standard error, SE=$1,931) vs $16,092 (SE=$1,573), p>0.05) and in mean number of events and expenditure for inpatient services, outpatient services, office-based visits, emergency room services, prescription drugs, and home health services (p>0.05). After adjusting for race/ethnicity, marital status, poverty category, smoking status, and comorbidities, the following expenditures were significantly (p<0.001) higher for women on AIs, compared to women on TMX: overall (62%; RR=1.62, 95% confidence interval (CI)=1.33-2.00) and for office-based visit expenditures (156%; RR=2.56, 95% CI=1.88-3.47), prescription drugs (75%; RR=1.75, 95% CI=1.33-2.32), and home health services (96%; RR=1.96, 95% CI=1.58-2.43). Number of office visits (35%; RR=1.35, 95% CI=1.17-1.56) and home health services use (19%; RR=1.19, 95% CI=1.13-1.26) were also higher for women on AIs compared to those on TMX (p<0.001). CONCLUSIONS: Among post-menopausal women with a history of breast cancer, being on an AI was associated with higher health-related expenditure, with office-based visits having the strongest influence.