OBJECTIVES: To estimate the total number of skeletal-related events (SREs), the associated hospital burden and direct medical costs when denosumab is used instead of zoledronic acid in patients with prostate cancer (PC) and bone metastases (BMs).  METHODS: A model was developed using the following data: country-specific PC mortality data from the World Health Organization or local registries; the proportion of PC patients with BMs from published literature; the prevalence of BMs in the metastatic PC population assuming a steady state approach (with mortality of metastatic disease equivalent to incidence); and the average survival of metastatic PC patients from published literature. Both the annual SREs rates from a European observational study and the treatment effect of denosumab versus zoledronic acid reported in a head-to-head clinical trial were used to predict the total number of SREs by treatment. Country-specific data from two multi-country observational studies were used to estimate the total number of hospitalisations, length of inpatient stays and direct medical costs associated with the management of SREs. RESULTS: Of the 67,375 patients with PC and BMs, the prevalence by country was: Austria, 2,447; Czech Republic, 2,707; Germany, 28,447; Greece, 3,888; Italy, 16,683; Spain, 9,428; and Switzerland, 2,776. If denosumab was the selected treatment option for all patients, an estimated 38,690 SREs per year could be avoided, leading to 14,599 fewer hospitalisations, a reduction of 270,007 inpatient days, and 155,213,984€ of savings in direct medical costs per year. The 2014 costs saved by country were: Austria, 19,919,201€; Czech Republic, 4,095,737€; Germany, 36,895,464€; Greece, 18,504,154€; Italy, 24,529,334€, Spain, 18,931,728€ and Switzerland, 31,338,666€.  CONCLUSIONS: Denosumab can result in significant reductions in the number and length of inpatient stays of PC patients with BMs, leading to substantial savings of direct medical costs associated with the management of SREs in each of the 7 European countries.