The aim of this study was to analyse the in vivo effect of a diet rich in extra-virgin olive oil and a fish-oil supplement on plasma and lipoprotein fatty-acid composition and on LDL susceptibility to oxidative modification in free-living Spanish male patients with peripheral vascular disease. A total of 12 patients were included in the experimental group which received extra virgin olive oil and a fish oil supplement (group OF). On the other hand, 13 patients which had refined olive oil as the main visible fat were considered as Control group. Plasma triglycerides decreased significantly after three months of dietary intervention. The LDL and plasma fatty-acid pattern in the group OF was characterized by a significant increase in n-3 polyunsaturated fatty acids, mainly 20:5 n-3 and 22:6 n-3. The slopes of LDL oxidative susceptibility were similar between baseline and endpoint values in both groups. However, the uptake of oxidized LDL by macrophages was significantly reduced in OF patients in comparison with the Control group. In conclusion, the daily intake of about 40 g/d of extra-virgin olive oil in combination with a daily supplement of 16 g of fish oil for 3 months in patients with peripheral vascular disease leads to a plasma-lipid profile less atherogenic than in patients having refined olive oil as the main visible food fat. The simultaneous consumption of alpha-tocopherol and natural antioxidants provided by extra-virgin olive oil seems to have a protective effect on the LDL susceptibility to oxidative modifications in spite of a higher proportion of n-3 polyunsaturated fatty acids.