e17042 Background: Prostate cancer (PC) is the most common cancer diagnosed among U.S. Veterans. Non-metastatic castration-resistant prostate cancer (nmCRPC) occurs in patients who, despite having received androgen deprivation therapy, experience a rising prostate-specific antigen (PSA) and castrate testosterone levels, with no evidence of metastatic disease on radiographic imaging. Given the recent approval of novel antiandrogens, the treatment landscape for nmCRPC has rapidly evolved. Although there have been numerous clinical trials examining the safety and efficacy of these treatments, few studies have identified real-world treatment patterns among nmCRPC patients. Methods: We conducted a retrospective observational study using patient information obtained from the Veterans Affairs (VA) Clinical Cancer Registry and the VA Corporate Data Warehouse (CDW) to identify patients who were diagnosed with PC at the VA, and later developed nmCRPC, defined as having: (1) evidence of rising PSA, i.e., 2 consecutive increases in PSA concentration over a baseline value; (2) evidence of ongoing androgen deprivation consisting of a serum testosterone level of ≤50 ng/dL (≤2.0 nmol/L); and (3) no evidence of metastatic disease on radiology reports. Treatments were extracted from CDW pharmacy dispensation records and were indexed at nmCRPC diagnosis. Results: A total of 12,549 patients were diagnosed with nmCRPC and treated in the VA from 2006 to 2020; of these, 7,239 (58%) were white, 3,386 (27%) were black, 784 (6%) were Hispanic, and 1,140 (9%) other. Median age at PC diagnosis was 69 years, with most patients residing in the South 4,817 (38%). Of the 7,659 (61%) patients receiving first-line (1L) nmCRPC therapy, 5,508 (72%) received bicalutamide, 621 (8%) ketoconazole, 563 (7%) abiraterone, 492 (6%) enzalutamide, and 242 (3%) flutamide. Although bicalutamide remained the most frequently used 1L nmCRPC therapy regardless of year, the adoption of abiraterone and enzalutamide beginning in 2012 resulted in a decline of 1L bicalutamide from 80% of patients in 2006 to 43% in 2020. Ketoconazole was the second most common 1L nmCRPC therapy and the most common second-line (2L) and third line (3L) nmCRPC therapy. Of patients receiving 1L therapy, 2,244 (31%) received 2L therapy, and of these, 708 (32%) received 3L therapy. Conclusions: To our knowledge, this is the largest real-world cohort of nmCRPC patients treated in a nationwide equal-access health care system. Despite the recent approval of several nmCRPC treatments (apalutamide, darolutamide, enzalutamide) which have demonstrated improved metastasis-free survival and treatment-related quality of life, our real-world findings suggest that older, first-generation antiandrogens remain the predominant 1L treatment for nmCRPC patients.