Background: About 2/3 of all prostate cancer (PCa) deaths occur in patients aged ≥75, who are frequently diagnosed with advanced PCa. ARSi abiraterone acetate (AA) and enzalutamide (E) are the most common 1^st line Rx for patients with mCRPC. Yet, the optimal treatment sequence for the elderly ≥75 after ARSi failure is still unclear. Methods: Using available medical records, patients aged ≥75 who started ARSi as 1^st line Rx for mCRPC within January 2015 - April 2019 and, upon progression, 2^nd line alternative ARSi or D were identified from the IRB approved hospital registries of 10 centers in Europe, North and South America. Patients were categorized by type of 2^nd line Rx for mCRPC into cohorts AA/E and D. Primary endpoints were overall survival (OS) from 1^st line AA/E start, OS and radiographic progression-free survival (rPFS) from 2^nd line Rx start, and safety. The Kaplan Meier method was used to calculate endpoint distributions and medians (95% CI). Results: Of the 122 patients identified, 57 (46.7%) had AA/E and 65 (53.3%) D, as 2^nd line Rx for mCRPC. Median follow-up was 26.3 months (95% CI, 23.1-27.9 months). Cohort AA/E tended to be older (81 vs 78 years; p=0.001) and with high-volume disease (45.5% vs 25.0%; p=0.022) compared to cohort D. No significant difference in OS from 1^st line ARSi onset and OS or rPFS from 2^nd line Rx start was found between the 2 cohorts. Cohort AA/E had longer rPFS than cohort D, albeit not significant (18.5 vs 12.0 months; p=0.13). Rates of adverse events (AEs) of any grade (42.1 vs 53.8; p=0.21) and AEs of grade ≥3 (19.3% vs 18.5%; p=1.0) did not show significant differences between the 2 cohorts. Conclusions: Within the limitations of small cohorts and retrospective design, treatment sequences with 2^nd line AA/E or D after failure of 1^st line alternative ARSi for mCRPC showed similar efficacy and safety in the elderly ≥75 years old.