Background: Prostate cancer (PCa) is a clinically heterogeneous disease and the incidence and mortality risk varies widely among racial/ethnic groups. Among Hispanic American (HA) men, PCa accounts for nearly one-quarter of the total cancer burden; in addition, advanced stage and mortality rates are significantly higher in HA compared to Non-Hispanic White (NHW) men. Despite a decade of declining overall incidence rates, incidence rates of advanced PCa appear to be increasing over time among HA men, a similar pattern seen among Non-Hispanic Blacks (NHB). Methods: Using the National Cancer Database, we identified patients with histologically confirmed prostate adenocarcinoma with reported race/ethnicity, clinical staging, Gleason score ≥ 6, and PSA at diagnosis between 2010 and 2016. HAs were divided into four major subgroups: Mexican/Chicano, Puerto Ricans, Cubans, and Central/South Americans. NHB, Asian, and other racial groups were excluded. Statistical analysis was derived from the Kruskal-Wallis test for continuous variables and χ² test for categorical variables. Univariable and multivariable logistic regression models were used to evaluate the association of HA ethnic subgroups with metastatic presentation and primary treatment. Results: A total of 428,829 patients were included with 5,625 (1.3%) being HA. Mexican comprised 51.2% of HAs and presented with higher PSA and Gleason score at diagnosis and more advanced cT, N1 and M1 stage when compared to NHW men and other HA subgroups (all, p < 0.001) (Table). After adjusting for age, PSA, year of diagnosis, cT, N, insurance, income, education, and performance score, Mexican had 1.32 (95%CI: 1.07-1.63, p = 0.01) higher odds of initial metastatic presentation and 0.68 (95%CI: 0.55-0.85, p < 0.001) lower odds of receiving treatment compared to NHW men while no statistically significant difference was seen for the other HA subgroups. Conclusions: Even after accounting for socioeconomic disparities, Mexican men present with a more aggressive disease when compared to NHW and other HA subgroups. Our results warrant further investigations into potential biological factors affecting HA PCa as well as identifications of potential barriers to treatment for vulnerable populations.