OBJECTIVES: Prostate Cancer patients using Androgen Deprivation Therapy (ADT) are considered at a higher risk for osteoporotic fractures due to excessive loss of bone mineral density (BMD). This study measured the incremental Cost Effectiveness (CE) of adding bisphosphonates to ADT based on QALYs gained. METHODS: A Markov model of fracture-risk associated with osteoporosis in patients with non-metastatic prostate cancer was developed to compare the incremental CE of adding pamidronate or zoledronic acid to ADT. Literature-based estimates of costs of treating osteoporotic fractures and average wholesale prices of bisphosphonates were used. Disutilities published by the National Osteoporotic Foundation for the first and subsequent year following an osteoporotic fracture were used to measure effectiveness of prescribing bisphosphonates. Robustness of assumptions was tested using deterministic and stochastic sensitivity analyses. RESULTS: The Markov analyses yielded total incremental cost of $17,009.40 for ADT + pamidronate and of $25,838.90 for ADT + zoledronic acid over ADT only option. Adding pamidronate resulted in a gain of 0.0128 QALYs at a marginal CE of $1,327,746 as compared to zoledronic acid which resulted in a gain of 0.015 QALYs at a marginal CE of $1,722,593. Monte Carlo simulation as well as one-way and two-way sensitivity analyses indicated robustness of the key assumptions such as probability of fracture, probability of death due to hip fracture and discount rate. CONCLUSIONS: In case of reducing the fracture-risk in non-metastatic prostate cancer patients using bisphosphonates resulted in nominal gain in QALYs at a very high marginal CEs for both drugs.