Background: Upfront docetaxel (UD) in castration-sensitive metastatic prostate cancer (CSPC) has improved failure-free and overall survival in the CHAARTED, GETUG-AFU 15 and STAMPEDE trials, resulting in a paradigm shift in practice patterns. However, the impact of docetaxel-based chemotherapy in underrepresented minority patients and in real-world practice remains to be described. The objective of this study was to evaluate toxicity and oncologic outcomes association with UD in an inner-city ethnically diverse CSPC cohort. Methods: We compared retrospectively collected clinical data for CSPC patients at Cook County Hospital treated with UD and androgen deprivation (UD, n = 49, 2013-17) to that of patients receiving androgen deprivation therapy alone (ADT, n = 49, 2010-17) using descriptive statistics and Cox Proportional Hazards analysis. Results: Median age was 59 years in UD and 60 years in ADT. African Americans, Hispanics and Caucasians formed 65%, 20%, and 10% in UD and 63%, 12% and 22% in ADT. Median (IQR) PSA at diagnosis was: UD 477 (91-1176) ng/ml, ADT 474 (54-1452) ng/ml (p = 0.7). Gleason score ≥ 7 was present in 79.4% in UD and 59% in ADT. UD and ADT had similar frequency of bone (92% vs. 96%, p = 0.3), visceral (16.3% vs. 14.3%, p = 0.7) and retroperitoneal nodal metastases (55% vs. 45%, p = 0.3). UD was initiated a median of 9 weeks from diagnosis. 94% in UD received > 3 cycles of chemotherapy. CTCAE grade > 3 events included anemia (6%); neutropenia (2%); infection (2%); diarrhea (4%); peripheral neuropathy (6%), and fatigue (2%). Median PSA nadir was 3.2 (0.5-18.6) vs. 2.95 (0.2-36.4) ng/ml and time to nadir was 30 (22-45) vs. 45 (20-77) weeks in UD vs. ADT. Biochemical progression was observed in 38.8% (UD) vs. 73.5% (ADT). Median time to progression was 73 weeks in UD vs. 88 weeks in ADT (HR: 0.9; 95% CI 0.5-1.6; p = 0.8). There were 8 deaths (UD: 2; ADT: 6) during a median follow-up of 57 (45-84, UD) and 123 (72.5-187, ADT) weeks. Conclusions: In a diverse, underserved population with CSPC, UD was well tolerated but was not associated with improvement in time to progression compared to ADT. These results warrant validation and underscore the importance of ensuring accrual of minorities in clinical trials.