In this study we investigated the effects on lipoproteins of medium chain fatty acids (MCFA) and myristic acid relative to those of oleic acid. Thirty-seven women and 23 men consumed a 3-wk run-in diet enriched in oleic acid followed by a 6-wk test diet rich in MCFA (n = 21), myristic (n = 20), or oleic acid (n = 19). Experimental fats were incorporated into solid foods. Total fat intake was 40 En% fat. The dietary compositions were the same except for 10 En%, which was provided by MCFA, myristic, or oleic acids, respectively. With the myristic acid diet, low density lipoprotein (LDL) cholesterol was 0.37 mmol/L higher compared with the oleic acid diet (P = 0.0064 for difference in changes). The MCFA diet increased LDL cholesterol, though not significantly, with 0.23 mmol/L relative to the oleic acid diet (P = 0.0752). Compared with the oleic acid diet, HDL cholesterol concentrations increased with the myristic acid diet by 0.10 mmol/L (P = 0.0273) but not with the MCFA diet. The MCFA diet slightly elevated triacylglycerol concentrations, but responses did not significantly differ between the diets. The MCFA diet significantly decreased the apoA-I to apoB ratio compared with both other diets (P < 0.02). We conclude that MCFA raise LDL cholesterol concentrations slightly and affect the apoA-I to apoB ratio unfavorably compared with oleic acid. Myristic acid is hypercholesterolemic, although less than predicted earlier, and raises both LDL and HDL cholesterol concentrations compared with oleic acid.