Lipid-lowering medications, particularly statins, may protect against aggressive prostate cancer. Fatal prostate cancer, the most clinically relevant outcome, remains understudied for this association. We prospectively studied lipid-lowering medication use and both incident and fatal prostate cancer in black and white men in the Atherosclerosis Risk in Communities (ARIC) study. A total of 6,518 men without cancer at visit 2 (1990-1992), the start of the statin era, were followed for prostate cancer incidence and death through 2012. Medication use was collected during study visits and telephone calls at up to nine time points during followup. Cox regression was used to estimate HR and 95% confidence intervals (CI) of total (white N ¼ 541, black N ¼ 259) and fatal (white N ¼ 56, black N ¼ 34) prostate cancer overall and by race. Lipid-lowering medication use was modeled as time-dependent current use or duration (never, <10, and 10 years). By visit 4 (1996-1998), 21% of white and 11% of black men had used a lipid-lowering medication, mostly statins. There was a suggestion that current users were less likely to die from prostate cancer than nonusers (HR ¼ 0.67, 95% CI ¼ 0.42-1.07) after multivariable adjustment. We observed no statistically significant differences between black and white men. Current use was not associated with incident prostate cancer, although long-term use was statistically significantly inversely associated with incidence (HR ¼ 0.68; 95% CI ¼ 0.50-0.92). Long-term lipid-lowering medication use was associated with lower risk of prostate cancer. Current use was possibly associated with fatal prostate cancer. Cancer Prev Res; 11(12); 779-88. 2018 AACR.