BACKGROUND: The purpose of the present work was to validate the MedDietScore by means of plasma fatty acid levels. METHODS: The study sample consisted of 189 men (44+/-13 years old) and 185 women (40+/-15 years old), randomly selected from the ATTICA study database. All participants completed a food frequency questionnaire (the EPIC-Greek FFQ), and a modified version of the MedDietScore (using weights) was then calculated to evaluate the level of adherence to the Mediterranean diet. Plasma and dietary fatty acids were measured. RESULTS: Correlation analysis revealed a strong positive relationship between the MedDietScore, monounsaturated fatty acids (P <0.001), monounsaturated fatty acids to saturated fatty acids (P <0.001), docosahexaenoic acid (22:6 n-3) (P <0.05) and n-3 fatty acids (P <0.001), and inverse correlations between the diet score and polyunsaturated fatty acids (comprised of the sum of n-3 and n-6 fatty acids) (P <0.001), saturated fatty acids (P <0.01), and total n-6 fatty acids (P <0.001). The effect size of the relationships between the weighted-MedDietScore and fatty acids was better than the relationships with the initial version of the diet score. CONCLUSIONS: Our findings suggest that the modified MedDietScore is a valid measure of various plasma fatty acids, and may prove a useful tool in assessing diet quality of adults.