Mediterranean diet has been related with reduced morbidity and better well-being. The aim of this study was to assess whether the adherence to the Mediterranean diet were associated with mental and physical health related to quality of life.This analysis included 11 015 participants with 4 years of follow-up in the SUN Project (a multipurpose cohort study based on university graduates from Spain). A validated 136-item food frequency questionnaire was used to assess the adherence to the Mediterranean diet at baseline, according to a nine-point score, presented in four categories (low, low-moderate, moderate-high and high). Health-related quality of life (HRQL) was measured after 4 years of follow-up with the Spanish version of the SF-36 Health Survey. Generalized Linear Models were fitted to assess adjusted mean scores, the regression coefficients (β) and their 95% confidence intervals (95% CIs) for the SF-36 domains according to categories of adherence to Mediterranean diet.Multivariate-adjusted models revealed a significant direct association between adherence to Mediterranean diet and all the physical and most mental health domains (vitality, social functioning and role emotional). Vitality (β=0.50, 95% CI=0.32-0.68) and general health (β=0.45, 95% CI=0.26-0.62) showed the highest coefficients. Mean values for physical functioning, role physical, bodily pain, general health and vitality domains were significantly better with increasing adherence to the Mediterranean diet. Those having improved their initial high diet scores have better scores in physical functioning, general health and vitality.Adherence to the Mediterranean diet seems to be a factor importantly associated with a better HRQL.