Background: The total cost of healthcare for patients with castration-resistant prostate cancer (CRPC) is an important component for assessing value of treatment options. The need for real-world evidence has increased with the introduction of oral targeted therapies for metastatic and nonmetastatic disease. In this study, we examined patient healthcare costs during periods of nonmetastatic CRPC (nmCRPC) and metastatic CRPC (mCRPC). Methods: This retrospective cohort study captured data from claims in the Truven Health MarketScan Commercial and Medicare Supplemental (Medigap) databases (1/1/2012?12/31/2016). Male patients (?18?years) with ?1 prostate cancer diagnosis, a subsequent metastatic diagnosis, and prescription claim for an mCRPC-indicated therapy (index date) were included. Patients were considered to have nmCRPC during the 12-month period prior to mCRPC if they had ?1 claim for androgen deprivation therapy. Unadjusted all-cause healthcare resource utilization (HRU) and associated costs in 2016 USD per patient per year (PPPY) were determined for nmCRPC and mCRPC periods. Results: Patients included from the Commercial database (N?=?449) had an average age of 59.4???4.5 (standard deviation) years and a mean Quan Charlson Comorbidity Index (QCI) score of 2.8???1.6. Among patients included from the Medigap database (N?=?1,173), the mean age was 78.6???7.2?years and mean QCI score was 3.3???2.0. Across all healthcare resource types, HRU was approximately 1.5?2.5 times greater after a diagnosis of metastasis for both study populations. For commercially insured patients, total all-cause healthcare costs increased 6.2-fold from the nmCRPC to mCRPC periods ($29,192 to $182,156 PPPY). Likewise, among Medigap patients, total all-cause healthcare costs increased 5.1-fold from the nmCRPC to mCRPC periods ($27,549 to $139,847). Conclusions: In this study, the cost of care during 2012?2016 was substantially higher for mCRPC than nmCRPC, underscoring the value of interventions that may delay progression to metastases in high-risk individuals.