To evaluate ascending aortic strain (AAS) with cardiac magnetic resonance (CMR) in a large consecutive series of patients with different types of cardiovascular disease (CVD).Two-dimensional phase-contrast gradient-echo sequences of the ascending aorta were retrospectively reviewed in 1027 patients (726 males, 301 females). Aortic lumen area was segmented using a semi-automatic approach to calculate AAS values. Subgroup analysis was performed for patients with normal CMR, tetralogy of Fallot (ToF), and ischemic heart disease (IHD). Multivariate and post-hoc analyses were performed to evaluate the effect of age, gender, and CVD on AAS values. Shapiro-Wilk, three- and two-way ANOVA, Mann-Whitney U, and Spearman correlation statistics were used.Multivariate analysis showed significant differences in AAS among decades of age (p0.001), genders (p=0.006) and CVD subgroups (p0.001) without interaction among these factors. A gender-related difference (higher AAS in females) was significant in ToF (p=0.008), while an AAS reduction during aging was observed in all CVD subgroups. Post-hoc analysis showed a significantly lower AAS in ToF and IHD patients compared to subjects with normal CMR (p0.001).Differences in age, gender, and CVD independently affect AAS. The lower AAS observed in ToF fosters its assessment during follow-up in adulthood. Future studies on causes and clinical implications of a higher AAS in females affected by ToF are warranted.