OBJECTIVES: To evaluate the incidence of skeletal-related events (SREs) in cancer patients with bone metastasis, their incremental direct costs and measure the potential economic value of the use of bisphosphonates. METHODS: A retrospective analysis of medical providers bills from 3.219 cancer patients (breast, prostate, lung, renal, multiple myeloma) for 24 private health care plans in Brazil was constructed and analyzed from the private payers perspective. Patient population was divided into two groups: placebo (2.431 patients with no use of bisphosphonate) and bisphosphonate (787 patients treated with Zometa®, Aredia®, Ostac® or Bonefós®). The total health care utilization cost per patient per year was calculated as the sum of the average pharmaceutical cost (bisphosphonate cost plus the cost of infusion, outpatient day hospital, materials and other prescription drugs) and the average cost per patient in treating a SRE, considering the real incidence for each bisphosphonate. SREs were defined as pathological bone fracture, spinal cord compression, radiation therapy to bone, and surgery to bone. RESULTS: The incidence of clinical and surgical SREs was: Zometa® (15%; 1%), Aredia® (19%; 2%), Ostac®/Bonefós® (26%; 13%), placebo (37%; 5%). The cost per patient in treating a clinical SRE, in USD, ranged from $58 to $2744. The cost per patient in treating a surgical SRE ranged from $610 to $21,250 (patient who required surgery to bone). The average cost per patient in treating a clinical SRE was $480 and in treating a surgical SRE was $5445. The total healthcare utilization cost per patient per year was the lowest for Zometa ($2106) followed by Aredia ($2375), Ostac/Bonefós ($2818) and placebo ($2637). CONCLUSION: Among the bisphosphonates analyzed, Zometa® showed to be effective at preventing the skeletal-related events with the lowest total health care utilization cost.