Introduction: Having an African ancestry is a well-established risk factor for advanced prostate cancer (PCa) and southern Africa has one of the highest mortality rates for PCa in the world. Meanwhile, southern Africa has the highest genetic diversity globally, and many ethno-linguistic groups reside in the region. However, no studies have investigated the significance of this diverse ethnical disparities with other epidemiological variables in risk of prostate cancer and its aggressiveness. Methods: This population-based study was performed as a part of the ongoing South African Prostate Cancer Study (SAPCS). We investigated a series of epidemiological risk factors including demographic and lifestyle factors in the participants (741 diagnosed PCa cases and 505 controls). Statistical methods were used to find the association of different variables with risk of PCa and the advanced disease. Results: Our findings suggest that the Nguni ethnicity is more likely than other ethnicities to be diagnosed with PCa (OR=1.63, 95% CI=1.02-2.63). Erectile dysfunction, gynecomastia and vertex/ complete baldness patterns were other risk factors associated with PCa. Subsequently, we have assessed factors associated with advanced PCa (ISUP=4/5), and showed that men of Tsonga ethnicity are significantly more likely to present with advanced diseases (OR=3.43 95% CI=1.62-7.27), even after adjustment for all covariates. Living in areas with higher poverty index was also associated with advanced PCa. Discussion: Studies to investigate the reason for the high prevalence of advanced PCa among men of African ancestry are lacking. This research revealed that African ethnicities are associated with advanced stage disease regardless of the epidemiological risk factors. Economic status showed to have a significant association not only for PCa, but also for disease aggression. These results can be improved by studies from other regions of sub-Saharan Africa with broad coverage of the population and alignment with genetic risk factors.