BACKGROUND: Previous studies found that global longitudinal strain is a superior predictor of mortality in male patients with heart failure with reduced ejection fraction (EF). This does not apply to women. Our aim was to investigate sex-specific differences in cardiac function and identify echocardiographic predictors of mortality in women with heart failure with reduced EF. METHODS AND RESULTS: Echocardiographic examinations were retrieved from 968 patients with heart failure with reduced EF (26.7% women). Images were analyzed offline, and the end point was all-cause mortality. During follow-up (median: 41 months) 163 patients (16.8 %) died. Women had significantly higher left ventricular (LV) EF (27.1% versus 25.4%, P=0.004), global longitudinal strain (-9.9% versus -8.9%, P<0.001), and global circumferential strain (-10.9% versus -9.7%, P<0.001). Moreover, women displayed higher E/e' (14.4 versus 13.0, P=0.004), LV diastolic elastance (1.16 versus 0.75, P<0.001), and lower e' (6.2 cm/s versus 6.9 cm/s, P<0.001). In women, tricuspid annular plane systolic excursion and LV isovolumetric relaxation time were significant predictors of outcome after multivariable adjustment (tricuspid annular plane systolic excursion: hazard ratio, 1.11; 95% CI, 1.04-1.18; P=0.003 per 1 mm decrease; isovolumetric relaxation time: hazard ratio, 1.07; 95% CI, 1.03-1.10; P=0.001 per 5 ms decrease). LVEF and global longitudinal strain were significant predictors in men (LVEF: hazard ratio, 0.94; 95% CI, 0.90-0.99; P=0.014 per 1% increase; global longitudinal strain: hazard ratio, 1.20; 95% CI, 1.04-1.38; P=0.013 per 1% decrease). CONCLUSIONS: Tricuspid annular plane systolic excursion and LV isovolumetric relaxation time provide prognostic information in women but not in men. Hence, in women with heart failure with reduced EF, right ventricular function, and LV diastolic function seem paramount in predicting mortality, whereas LV systolic function is more important in men.