AbstractCardiometabolic diseases (CMDs) are a major cause of mortality worldwide, yet men and women present remarkable differences in disease prognosis, onset and manifestation. Here we characterize how sex differences in cardiometabolic risk factors vary with age by examining 45 phenotypes and 6 lifestyle factors in 146,021 participants of the Dutch population cohort Lifelines. We show that sex differences are present in 71% of the studied phenotypes. For 31% of these phenotypes, the phenotypic difference between sexes is dependent on age. CMD risk factors show various patterns of age-related sex differences, ranging from no difference for phenotypes such as body mass index (BMI) to strong age-modified sex differences for lipid levels. We also identify lifestyle factors that influence phenotypes in a sex- and age-dependent manner. These results highlight the importance of taking age into account when studying sex differences in CMDs.