Abstract Background: Cholesterol reduction is considered a mechanism through which lipid-lowering drugs including statins are associated with a reduced aggressive prostate cancer risk. While prior cohort studies found positive associations of total cholesterol with advanced stage and grade in White men based mostly on cholesterol at baseline, whether associations for total cholesterol, low (LDL)- and high (HDL)-density lipoprotein cholesterol, apolipoprotein B (LDL particle component) and A1 (HDL particle component), and triglycerides exist for fatal prostate cancer and in Black men using time-updated biomarkers is unknown. Methods: We conducted a prospective study of 1,553 Black and 5,071 White cancer-free men attending visit 1 (1987-1989) of the Atherosclerosis Risk in Communities Study. Death from prostate cancer was ascertained from the underlying cause on death certificates. Follow-up began at visit 1 and ended at date of death, loss to follow-up, or 12/31/2018, which ever came first. There were 128 deaths from prostate cancer (43 in Black men, 85 in White men) ascertained over 153,184 person years of follow-up (mean 23 years). We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for fatal prostate cancer per 1-standard deviation increment and for tertiles (T1-T3) of time-updated lipid biomarkers adjusting for baseline age, education, race and field center, and updated BMI, waist circumference, smoking status, hyperglycemia and diagnosed diabetes, aspirin use, and lipid-lowering drug use overall, and in Black and White men. Results: Higher total cholesterol concentration was associated with higher fatal prostate cancer risk in White men only (HR per-1 SD=1.25; 95%CI=1.00-1.58), and higher concentration of LDL cholesterol appeared to be associated with fatal prostate cancer in White men only (HR per-1 SD=1.26; 95%CI=0.99-1.60). Apolipoprotein B was non-linearly associated with fatal prostate cancer overall (T2 vs. T1 HR=1.66; 95% CI=1.05-2.64) and in Black men (T2 vs. T1 HR=3.59; 95% CI=1.53-8.40) but not in White men (T2 vs. T1 HR=1.13; 95% CI=0.65-1.97). HRs were >1 overall (T3 vs. T1 HR=1.18) and in Black men (T3 vs. T1 HR=2.11) but were not statistically significant. HDL-cholesterol, Apolipoprotein A1 and triglycerides were not associated with fatal prostate cancer overall and by race. Tests for statistical interaction by race were not statistically significant. Conclusion: Positive associations with fatal prostate cancer were observed with total and LDL-cholesterol in White men, and apolipoprotein B in Black men. These findings may improve the understanding of lipid metabolism in prostate carcinogenesis, and further emphasize the importance of cholesterol control. Support: NHLBI contracts, NCI grants, NPCR Citation Format: Michael T. Marrone, Anna E. Prizment, David Couper, Kenneth R. Butler, Brad C. Astor, Corinne E. Joshu, Elizabeth A. Platz, Alison M. Mondul. Total, LDL-, HDL-cholesterol, apolipoproteins, and triglycerides and risk fatal prostate cancer in black and white men in the ARIC study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB158.