Background: Evidence on the association between Mediterranean diet (MedDiet) adherence and cognition is presently inconsistent. Objectives: The aims of this study were to investigate the association between midlife MedDiet adherence and cognitive performance assessed 13 y later among participants in the SU.VI.MAX (Supplementation with Vitamins and Mineral Antioxidants) study and to test the hypothesis of effect modification by occupation and education as cognitive reserve markers. Design: A Mediterranean Diet Score (MDS) and a Mediterranean-Style Dietary Pattern Score (MSDPS) were estimated by using repeated 24-h dietary records (1994-1996) from 3083 middle-aged subjects. Cognitive performance was assessed in 2007-2009 by using 6 neuropsychological tests, and a composite score was built. Subgroup analyses were performed according to occupational and educational status. Mean differences and 95% CIs were estimated through covariance analyses. Results: After potential confounders were accounted for, no association between MDS or MSDPS and cognitive scores was detected except for a lower phonemic fluency score with decreasing MSDPS (P = 0.048) and a lower backward digit span score with decreasing MDS (P = 0.03). In turn, a low MDS was related to a lower composite cognitive score in the small subsample of manual workers (n = 178, P-interaction = 0.04) who could be hypothesized to have low cognitive reserve. MedDiet adherence did not interact with educational level in relation to cognitive function. Conclusion: This study did not find support for a beneficial effect of MedDiet adherence on cognitive function, irrespective of educational level, which is the strongest indicator of cognitive reserve. This trial was registered at clinicaltrials.gov as NCT00272428. Am J Clin Nutr 2013;97:369-76.