Background: Over 10% of men with metastatic prostate cancer (PC) have germline DNA damage response gene alterations; most studies have reported BRCA2 alone or an aggregate of BRCA1, BRCA2 and ATM. Emerging data suggest ATM mutations have distinct effects and warrant individual gene evaluation. We hypothesize that, compared to patients (pts) carrying germline BRCA2 mutations (gBRCA2mut), pts carrying germline ATM mutations (gATMmut) may have different treatment response to androgen-receptor-targeted agents, docetaxel, platinum therapy and PARP inhibitors (PARPi). Methods: This is an international, multicenter, retrospective case-control study of pts with PC who underwent clinical germline genetic testing between 2014-2019. We identified pts with gATMmut and matched pts with gBRCA2mut by stage at diagnosis and year of testing. IRB-approved medical records review, χ² and log rank tests were performed. Results: 39 gATMmut cases and 39 matched gBRCA2mut cases were identified for total of 78. A third (13/39) of pts in each cohort had metastases at diagnosis. Of those diagnosed with localized stage, 81% (21/26) of gATMmut and 73% (19/26) of gBRCA2mut developed metastasis (median times to metastasis 69 vs 49 months, respectively (p=0.1)). Pts in gATMmut and gBRCA2mut cohorts had similar age, Gleason grade, and PSA at diagnosis. We did not observe a difference in PSA₅₀ response rates to abiraterone, enzalutamide, docetaxel, or carboplatin for mCRPC (Table). gBRCA2mut pts were more likely to respond to PARPi for mCRPC; where available, somatic loss of heterozygosity (LOH) data will be reported at final presentation. Conclusions: While response to standard therapies appears similar between gATMmut and gBRCA2mut cohorts, response to PARPi in gATMmut appears to be attenuated compared to gBRCA2mut. More studies are needed and pts with gATMmut warrant prioritization for novel treatment strategies.