The first aim of this study was to explore the relation between cognitive reserve, age, and neuropsychological functioning in a healthy sample; and second, to determine the risk of showing cognitive deficits as a function of cognitive reserve. One hundred forty-six healthy participants between the ages of 20 and 79 were submitted to neuropsychological assessment, focusing on attention, memory, visuo-construction, conceptualization and reasoning. Premorbid IQ as measured with the Wechsler Adult Intelligence Scale Vocabulary subtest was used as a proxy of cognitive reserve. Multivariate regression analysis with age and premorbid IQ as explanatory factors revealed a significant effect in all neuropsychological tests. Logistic regression revealed that participants with low cognitive reserve were more likely to obtain deficient scores (< or =1.5 SD below the mean) in the cognitive domains of attention (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.059.29), memory (OR, 6.17; 95% CI, 1.69-22.61) and global functioning (OR, 6.44; 95% CI, 2.56-16.22) than participants with high cognitive reserve. Results suggest that cognitive reserve acts as a protective factor against the expression of cognitive decline related to age in healthy individuals.