We examined associations between dietary fatty acids and progression of coronary artery disease (CAD) in 50 men receiving a lipid-lowering diet or usual care in the St Thomas' Atherosclerosis Regression Study. Nutrient intake was assessed by dietary history and computerized food tables. Progression of CAD over 39 mo, measured by a decrease in minimum absolute width of coronary segments (MinAWS) on angiography, was highly correlated with intakes of palmitic, stearic (18:0), palmitoleic, and elaidic (t-18:1) acids (P < 0.001); no protective effects were found with polyunsaturates. Total saturates and trans unsaturates explained 20% of variance in CAD progression. After adjustment for plasma cholesterol and other risk factors, change in MinAWS was most closely associated with intakes of 18:0 and t-18:1 fatty acids (P = 0.009). We suggest that progression of CAD in men is strongly related to intakes of both long-chain saturates and trans unsaturates, the effects of 18:0 and t-18:1 possibly being independent of plasma cholesterol concentration.