As the female population continues to live longer past menopause, healthcare providers need to establish a proactive approach to the management of the menopausal population in order to reduce long-term healthcare expenditures. OBJECTIVE: The purpose of this analysis is to assess the cost-effectiveness of hormone replacement therapy (HRT) in peri-menopausal women of Belgium and the United Kingdom. METHODS: A Markov model was constructed to model treatment pathways and outcomes of two cohorts. The model compares the health and economic outcomes of women from age 53 through 94 treated with HRT versus those not treated with HRT. The following health states were considered in the model: well, osteoporosis- related fractures, coronary heart disease, stroke, Alzheimer s disease, breast cancer, diabetes and death. A clinical management analysis determined health care utilization for each health state , while published epidemiologic estimates from each country, incorporating relative risk ratios, incidence and mortality rates for each health state were entered into the model. A resource valuation using country-specific inpatient and outpatient costs were calculated for each health state . RESULTS: Cost-effectiveness was measured as the incremental cost-per-life-year gained and the incremental cost per event avoided. Assuming full compliance with treatment in the HRT cohorts, the results for Belgium and the United Kingdom indicate significant reductions in episodes of disease. Furthermore, lifetime expected costs per patient in the treated cohort decreased with age while the lifetime costs of the untreated cohort increased with age. A Monte Carlo analysis tested the sensitivity of the model results. CONCLUSIONS: Hormone replacement therapy is a more cost-effective means of disease prevention when compared to no treatment and should be considered by healthcare providers in Belgium and the United Kingdom in the health management of peri-menopausal populations.