Higher risk for prostate cancer (PCa) among African Americans is partly associated with exposure to dietary fatty-acids, the carcinogenic effects of which remain controversial. Odds ratio of PCa risk was determined by unconditional logistic regression comparing highest with lowest quartiles of plasma fatty-acids in a case-control design. Mean age for 173 African Americans and 340 Nigerians was 56.9 ± 9.8 and 60.1 ± 14.0, p<.006, median (25th, 75th percentile) plasma fatty-acid was 2598 (2306, 3035) μg/ml and 2420 (2064, 2795) μg/ml, p<.001, with 48 (27.7%) and 66 (19.4%) PCa cases, respectively. African Americans recorded higher total, omega-6, and trans, but lower saturated and omega-3 fatty-acids, with non-significant PCa risk association for total, omega-6 and trans fatty acids. Positive PCa risk trend was observed in both populations with nervonic, erucic, and arachidonic acids, with docosahexaenoic acid (DHA) among African Americans, and with behenic and stearic acids in Nigerians. Non-significant negative PCa risk trend was observed with ecosapentaenoic acid (EPA) in Nigerians only. These preliminary findings need to be further explored in a larger study that will include risk analysis of fatty-acid ratios to clarify their combined impact on PCa risk.