Epigenomic differences between men and women must be taken into account when designing and analysing future studies, say the authors of a recent epigenome-wide association study. Singmann et al. analysed autosomal DNA methylation levels in whole-blood samples taken from 1,799 European men and women and found that 1,184 CpG sites were differentially methylated between men and women across all autosomes. Some of the differentially methylated loci also exhibited differential gene expression between men and women, while some were enriched among imprinted genes. Findings were replicated in three independent European cohorts. The finding of substantial epigenomic differences between men and women, combined with previous studies that have shown divergence between males and females with respect to disease risk and incidence, highlight the importance of considering gender in study designs and analyses.