Background: Approximately 5-10% of men with prostate cancer (PC) are eligible for treatment with PARP inhibitors. As an estimated 120,000 men living in the US have metastatic PC, between 6,000-12,000 men may be eligible for treatment with PARP inhibitors. Recently, several PARP inhibitors have been approved as single or combination therapies in the first-line castrate-resistant (CR) setting and later-line setting including: olaparib, olaparib plus abiraterone (AAP), and talazoparib plus enzalutamide. It is unclear if these newly approved therapies may be cost prohibitive for patients and/or health care systems. Methods: Using average sale price data from UpToDate for PARP inhibitors and novel hormone therapies (NHTs), we calculated the total cost of treatment for each single or combination therapy regimen. We used phase II/III clinical trial data to determine the median duration of treatment for each regimen. Results: The three approved PARP inhibitors have total costs in descending order as follows: AAP plus olaparib ($689,813.77), talazoparib plus enzalutamide ($388,390.46), and olaparib ($202,845.22). In comparison, in the PROfound trial, the cost of AAP alone was $192,140.37 and in the TALAPRO-2 trial, the cost of enzalutamide alone was $ 253,780.80. The difference in estimated cost between olaparib plus AAP versus talazoparib plus enzalutamide per patient is $37,970.29. Conclusions: Despite several new approved therapies in BRCA mutated and HRR mutated mPC, the total costs for PARP inhibitors remain prohibitive for health care institutions. The estimated difference between two newly approved PARP plus NHT regimens could translate in a difference of $455,643,480 in healthcare system costs if all eligible U.S. men received treatment with olaparib plus AAP over talazoparib plus enzalutamide.