We aimed to investigate sex-related differences in left ventricular deformation in heart failure with reduced ejection fraction (HFrEF) patients with comorbid hypertension (HTN) by cardiac MRI. A total of 281 patients with HFrEF who underwent cardiac MRI were enrolled in this study. Sex-related differences in left ventricular (LV) structure, function and strains derived from cardiac cine MRI in the context of HTN were measured and compared. The clinical variables associated with LV strains in HFrEF patients with comorbid HTN and determinants of impaired LV strains were investigated for both sexes. The prevalence of HTN did not differ between the sexes (P > 0.05). Despite having a similar LVEF, hypertensive men displayed decreased LV deformation in all three directions compared with hypertensive women (all P < 0.05). Male sex and its interaction with HTN were associated with higher LV mass index, reduced LV GCPS and GLPS compared with hypertensive women (all P < 0.05). Male sex was associated with LV deformation impairment in hypertensive HFrEF patients (all P < 0.05). After adjustment for covariates in HFrEF patients, HTN was found to be an independent determinant of impaired LV GCPS [β = 0.17; P = 0.022] and GLPS [β = 0.25; P < 0.001]) in men but not in women (all P > 0.05). Sex had a modifying effect on LV deformation in hypertensive HFrEF patients, with greater adverse effects on LV strains in men than in women. Sex-tailored treatment approaches may be considered in the future for HFrEF patients with comorbid HTN.Copyright © 2023. Published by Elsevier Inc.