Background <p>Cognitive processes are essential for efficient daily functioning. Demographic factors such as age and education influence cognitive performance. However, the impact of sex on cognition is less understood and previous research has reported inconsistent findings. We investigated sex differences in cognitively unimpaired adults in three cohorts, using two complimentary approaches: a univariate approach to compare direct performance across cognitive domains and the multivariate approach of graph theory to compare global and nodal features as well as the modular organization of cognitive connectomes.</p> Methods <p>We included 4,259 cognitively unimpaired participants (334 from the GENIC cohort, 3,703 from the National Alzheimer’s Coordinating Center [NACC], and 222 from the Alzheimer’s Disease Neuroimaging Initiative [ADNI]). Cognitive variables were corrected for age and education, and cognitive connectomes were constructed using Spearman correlation coefficients. Sex differences in cognitive performance were examined through ANCOVAs as well as global and nodal network measures.</p> Results <p>Univariate analyses showed significant sex differences in three out of five cognitive domains across cohorts, mainly of small effect sizes. Graph theory analyses revealed minimal sex differences in cognitive module organization and no significant differences on global network measures, except for a higher modularity observed in women compared to men in the NACC. In contrast, nodal analyses revealed sex differences in several network measures.</p> Conclusions <p>Sex differences in cognition seem to be of small effect size and limited to specific cognitive domains or cognitive variables, while the overall organization and global features of cognitive connectomes were largely comparable between men and women. Future studies should clarify whether men and women may rely on slightly different cognitive strategies to approach cognitive tasks without overt differences in cognitive ability.</p>