We sought to correlate real-world outcomes on NHT with comprehensive genomic profiling (CGP)-reported alterations, hypothesizing that AR amplification (ARamp) and deleterious genomic alterations (GAs) in BRCA2, PTEN, RB1, TP53 would correlate with worse outcomes on NHT. Abiraterone (n = 242; 61%) and enzalutamide (n = 145; 39%) were most common NHTs. As hypothesized, ARamp correlated with worse TTD (aHR: 3.37 [1.26-9.0]) and OS (aHR: 4.92 [1.47-16.5]). BRCA2 GA correlated with improved OS (aHR: 0.41 [0.21-0.81]), but no differences in TTD (aHR: 1.25 [0.82-1.9]). RB1 GA had trends for worse OS (aHR: 2.0 [0.93-4.28]) and worse TTD (aHR – 1.41 [0.72-2.8]). TP53 GA had worse OS (aHR: 1.47 [1.1-2.0]), but no difference in TTD (aHR: 1.08 [0.85-1.4]),...ARamp is associated with worse TTD and OS in mCRPC pts treated with NHT in real-world. Surprisingly, BRCA2 GA correlated with improved OS but not TTD.