Background: Combination therapies using the androgen deprivation therapy (ADT) backbone have revolutionized treatment of metastatic hormone sensitive prostate cancer (mHSPC). Combinations include ADT plus docetaxel (DOC) or the androgen receptor targeting agents (ARTAs) abiraterone (AA), enzalutamide (ENZ), apalutamide (APA), and darolutamide (DAR). This study evaluates the utilization of these therapies in de novo mHSPC in a cohort of veterans and assesses recent overall survival (OS) of these therapies. Methods: Veterans were identified from 2012-2021 in the Veterans Affairs Prostate Cancer Data Core (VAPC) and oncology tumor registries using the initial pathological diagnosis of prostate cancer with SEER stage ‘distant’. All veterans had ADT initiated within 1 month prior and 3 months after diagnosis in VAPC. Additional therapies including DOC or ARTAs were collected from VAPC if initiated from 1 month prior to 4 months after ADT initiation. Data cut point was June 2022. Results: 5,006 patients with de novo mHSPC were identified with median age of 73.1 years (yrs), and 1338 (26.7%) identified as Black race. From 2012 to 2021, ADT alone was used in 3,569 (71.3%) of veterans, DOC in 438 (8.7%) and ARTAs in 999 (20.0%), wherein use of different ARTAs was AA in 783 (78.4%), ENZ in 204 (20.4%), APA in 10 (1.0%), and DAR in 2 (0.2%). Use of combination therapy for mHSPC increased from 3.1% in 2012-2013 to 61.2% in 2020-2021. Use of DOC peaked in 2016 and was used in 16.3% of veterans that year. Veterans treated with DOC were significantly younger (median 67.3 yrs, p<0.001) compared to veterans treated with ARTAs (73.1 yrs) or ADT alone (74.3 yrs). Veterans treated with combination therapies had longer median OS compared to ADT alone (37.2 vs. 29.3 months, p<0.001), with no significant difference between DOC and ARTA combinations (p=0.84). For 2,042 veterans with de novo mHSPC treated from 2018-2021, median OS of veterans treated with ADT+DOC (n=161, 35.3 months) and ADT+ARTA (n=849, 41.2 months) was longer than ADT alone (n=1,032, 29.3 months, p<0.001). There was no significant difference in median OS between DOC and ARTA combinations in this group (p=0.69). Conclusions: In veterans presenting with de novo mHSPC, use of initial combination therapy has increased, with the majority of veterans treated with ADT and an ARTA in 2020-2021. In this cohort, combination therapy was associated with longer OS compared to ADT alone and no significant differences were found between type of combination and OS.