OBJECTIVES: To estimate the total number of skeletal-related events (SREs) prevented, related hospital burden and direct medical expenditure when denosumab is used instead of zoledronic acid for SRE prevention in seven European countries. METHODS: A model was developed combining country-specific breast cancer mortality data from the World Health Organization or from local registries, the proportion of metastatic breast cancer patients with bone metastases (BMs) at high risk of developing SREs from published literature, the prevalence of breast cancer with BMs was derived assuming a steady state approach (with incidence equivalent to mortality of metastatic disease), and the average survival for metastatic breast cancer patients from published literature. Annual SRE rates from a European observational retrospective study and the treatment effect observed in a head-to-head clinical trial of denosumab versus zoledronic acid were used to estimate the total number of predicted SREs by treatment option. Country-specific findings from two retrospective studies were used to estimate the total number of hospitalisations, inpatient days and direct medical costs associated with the management of SREs.  RESULTS: Across all countries, the estimated prevalence of breast cancer patients with BMs was 87,592 patients: Austria, 3,253; Czech Republic, 3,509; Germany, 37,895; Greece, 4,639; Italy, 27,767; Spain, 7,553; and Switzerland, 2,975. When denosumab was the selected treatment option, 36,324 SREs were estimated to be avoided per year compared with the use of zoledronic acid, which would save 24,110 hospitalisations, 536,551 inpatient days and 206,605,754€ of direct medical costs (2014 costs in €: Austria, 23,890,554; Czech Republic, 5,779,856; Germany, 60,659,628; Greece, 15,941,728; Italy, 39,998,970; Spain, 17,249,548; and Switzerland, 43,085,469).  CONCLUSIONS: Denosumab’s clinical superiority in the prevention of SREs over zoledronic acid could result in significant savings in the number and duration of hospitalisations, reducing direct medical costs associated with the management of SREs in Europe.