OBJECTIVES: Approximately 2.8 million American men have a history of prostate cancer, the most prevalent cancer among men in the US. This study quantified the effects of prostate cancer on direct health care costs to insurers and patients. METHODS: Using data 1996-2009 from the Medical Expenditure Panel Survey (MEPS), a large, nationally-representative database from the US, this study performed multivariate analyses of the relationship between prostate cancer and direct annual health care costs to insurers and patients, at individual and US aggregate levels. All men age 40 and older with International Classification of Disease Codes, 9threvision of 185 were identified. RESULTS: The MEPS database included 1,399 patients with prostate cancer.  Mean age was 72 years, and 71% were Caucasian.  Prostate cancer patients incurred $9,300 more in overall annual health care costs per patient when compared to non-prostate cancer patients ($18,423 vs. $9,093).  The majority of direct health care costs were borne by the insurer ($8,900) rather than the patient ($430). Prostate cancer had a larger effect on incremental costs for younger patients ($16,253 40-64 years vs. $10,236 65-74 years; $7,767 75+ years).  When aggregated to the US population, prostate cancer accounted for an incremental annual cost of $14.27 billion.  The largest aggregate costs were incurred by patients aged 40-64 years ($5.33 billion), compared to those aged 65-74 ($4.86 billion) and patients aged 75+ ($4.08 billion). CONCLUSIONS: These findings indicate that the cost burden from prostate cancer is quite large.  Younger patients incur more direct health care costs, possibly due to more aggressive treatment practices, which may be related to more aggressive tumor burden.  With aging of the population, prevalence of prostate cancer is expected to increase to 3.2 million in the US in 2020.  Further research to understand these cost implications is warranted.