Background: Prospective studies suggest that abiraterone (Abi) use in mCRPC is associated with improved progression-free survival in African-American (AA) patients (pts) compared to non-Hispanic White (NHW) pts. It is unclear whether racial disparities in Abi effectiveness exist for pts with mCRPC treated in real-world practice. Methods: In this retrospective cohort study, we used the nationwide Flatiron Health electronic health record-derived de-identified database to select pts who received first-line (1L) systemic therapy for mCRPC between January 1, 2012 and December 31, 2018. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression models of comparative effectiveness, using age, race, comorbidity index, prostate-specific antigen (PSA), baseline steroid or opioid use, insurance status, practice type, practice Abi prescribing rate, and practice region as covariates. The primary exposure was treatment with 1L Abi. Overall survival (OS) was the primary outcome, and time-to-next-treatment (TTNT), using Fine-Gray models with death as a competing risk, was the secondary outcome. Racial disparities between Abi vs. no Abi groups were explored with stratified analyses by race and race-treatment interaction terms. Results: Of 3808 pts, 1729 (45.4%) received 1L Abi, 1255 (33.0%) received 1L enzalutamide, and 549 (14.4%) received 1L docetaxel. The cohort included 2165 (68.7%) NHW and 404 (10.6%) AA pts. Pts receiving Abi were older (mean age 74 vs. 72) and more likely to be treated at academic centers (8% vs. 6%) than pts not receiving Abi. Among pts receiving Abi, AAs had improved OS compared to NHWs (Table). Compared to receipt of a non-Abi regimen, receipt of Abi was not associated with OS among AA pts but was associated with decreased OS among NHW pts. A significant race-by-treatment interaction for OS existed among patients receiving 1L Abi (interaction coeff = 0.27 95% CI = 0.02-0.53). There were no race-based disparities found in TTNT. Conclusions: In a large real-world analysis of pts who received 1L systemic therapy for mCRPC, AAs who received Abi had improved OS compared to NHWs – a finding consistent with ABI-RACE (NCT01940276). Among NHW pts, 1L Abi was associated with decreased OS. These real-world data suggest race-based differences in therapeutic response to Abi and future prospective evidence is needed to assess drivers of differential Abi efficacy in mCRPC.