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 regimens in minorities and in real-world practice remains to be described. The objective of this study is to evaluate tolerability and response to UD in an inner-city ethnically diverse CSPC cohort. Methods: We retrospectively reviewed clinical data for CSPC patients at Cook County Hospital. Patients treated with UD and androgen deprivation (UD, n = 49, 2013-17) were compared to those receiving androgen deprivation alone (ADT, n = 42, 2010-17) using descriptive statistics and Cox Proportional Hazards analysis. Results: Median age was 59 and 60 years in UD and ADT, respectively. African Americans, Hispanics and Caucasians formed 69%, 18%, and 10% in UD and 64%, 9.5% and 26% in ADT. Median PSA at diagnosis was: UD 536 [72-1110] ng/ml, ADT 229 [54-999] ng/ml (p = 0.3). Gleason score > 7 was present in 89.8% [UD] and 92.8% [ADT]. UD and ADT had similar frequency of bone (91% vs. 95%, p = 0.5), visceral (12.2% vs. 11.9%, p = 0.9) and retroperitoneal nodal metastases (55% vs. 45.2%, p = 0.3). UD was initiated a median of 8 weeks from diagnosis. 94% in UD received > 3 cycles of chemotherapy. CTCAE grade > 3 events included anemia (6%); neutropenia (6%); infection (4%); diarrhea (4%); peripheral neuropathy (6%), and fatigue (2%). Median PSA nadir was 3.2 [0.5-40.1] vs. 3.45 [0.1-36.4] ng/ml and time to nadir was 20 [13-27] vs. 41 [19-69] weeks in UD vs. ADT. Biochemical progression was observed in 34.7% [UD] vs. 40.5% [ADT]. Median time to castration-resistance was UD: 39 [31-67] vs. ADT: 65 [34-76] weeks [HR: 0.9; 95% CI 0.4-1.8; p = 0.7]. There were 12 deaths [UD: 4; ADT: 8] during a median follow-up of 46 [23-86, UD] and 111 [68-157, ADT] weeks. Conclusions: In a diverse underserved population with CSPC, UD was well tolerated but was not associated with improvement in time to castration compared to ADT. These results warrant validation and underscore the importance of ensuring accrual of minorities in clinical trials.