This study tries to find detectable signals of gene flow of Sub-Saharan origin into the Mediterranean in four genomic regions previously associated with coronary artery disease. A total of 366 single-nucleotide polymorphisms were genotyped in 772 individuals from 10 Mediterranean countries. Population structure analyses were performed, in which a noticeable Sub-Saharan component was found in the studied samples. The overall percentage of this Sub-Saharan component presents differences between the two Mediterranean coasts. D-statistics suggest possible Sub-Saharan introgression into one of the studied genomic regions (10q11). We also found differences in linkage disequilibrium patterns between the two Mediterranean coasts, possibly attributable to differential Sub-Saharan admixture. Our results confirm the potentially important role of human demographic history when performing epidemiological studies.