Background : The strong correlation between national consumption of fat and national rate of mortality from prostate cancer has raised the hypothesis that dietary fat increases the risk of this malignancy. Case-control and cohort studies have not consistently supported this hypothesis. Purpose : We examined prospectively the relationship between prostate cancer and dietary fat, including specific fatty acids and dietary sources of fat. We examined the relationship of fat consumption to the incidence of advanced prostate cancer (stages C, D, or fatal cases) and to the total incidence of prostate cancer. Methods : We used data from the Health Professionals Follow-up Study, which is a prospective cohort of 51529 U.S. men, aged 40 through 75, who completed a validated food-frequency questionnaire in 1986. We sent follow-up questionnaires to the entire cohort in 1988 and 1990 to document new cases of a variety of diseases and to update exposure information. As of January 31, 1990, 300 new cases of prostate cancer, including 126 advanced cases, were documented in 47855 participants initially free of diagnosed cancer. The Mantel-Haenszel summary estimator was used to adjust for age and other potentially confounding variables. Multiple logistic regression was used to estimate relative risks (RRs) when controlling simultaneously for more than two covariates. Results : Total fat consumption was directly related to risk of advanced prostate cancer (age- and energy-adjusted RR = 1.79, with 95% confidence interval [CI] = 1.04–3.07, for high versus low quintile of intake; P [trend] =.06). This association was due primarily to animal fat (RR = 1.63; 95% CI = 0.95–2.78; P [trend] =.08), but not vegetable fat. Red meat represented the food group with the strongest positive association with advanced cancer (RR = 2.64; 95% CI = 1.21–5.77; P =.02). Fat from dairy products (with the exception of butter) or fish was unrelated to risk. Saturated fat, monounsaturated fat, and α-linolenic acid, but not linoleic acid, were associated with advanced prostate cancer risk; only the association with α-linolenic acid persisted when saturated fat, monounsaturated fat, linoleic acid, and α-linolenic acid were modeled simultaneously (multivariate RR = 3.43; 95% CI = 1.67–7.04; P [trend] =.002). Conclusion : The results support the hypothesis that animal fat, especially fat from red meat, is associated with an elevated risk of advanced prostate cancer. Implications : These findings support recommendations to lower intake of meat to reduce the risk of prostate cancer. The potential roles of carcinogens formed in cooking animal fat and of a-linolenic acid in the progression of prostate cancer need to be explored. [J Natl Cancer Inst 85: 1571–1579, 1993]