Heart failure with preserved ejection fraction (HFpEF) is common and primarily affects older females. Once considered a disease of diastolic dysfunction, it is now understood to be a complex condition involving cardiac abnormalities and alterations in arterial function. HFpEF is twice as common in females than in males, but the reasons for this are not fully understood. Sex differences in arterial structure and function may account for some of these observations. In this brief review, we discuss how alterations in arterial structure and function contribute to HFpEF pathophysiology specifically in females and demonstrate that, in females, HFpEF is an arterial disease.