The Apolipoprotein E (ApoE) ε4 allele is a major genetic risk factor for sporadic Alzheimer's disease and has been associated with structural and functional brain alterations across the adult life span. Recent studies have presented evidence that ε4 affects microstructural properties of brain white matter (WM) in non‐demented carriers of the ε4 allele, but conflicting evidence has been presented as well. The main purpose of the present study was therefore to examine ApoE effects on WM in a large sample of middle‐aged and older adults (N = 273). Diffusion tensor imaging (DTI) data was acquired, and tract‐based as well as voxel‐wise analyses were conducted. The tract‐based analyses revealed no significant ApoE effects, and no significant interactions between genotype and age were observed. Taken together, the findings of the present study suggest that ApoE effects on white‐matter microstructure are less abundant than has been suggested in some previous studies.