Early systolic lengthening and postsystolic shortening may yield prognostic information in cardiovascular high-risk groups. We aimed to investigate the prognostic potential of these patterns in patients with heart failure with reduced ejection fraction (HFrEF), and specifically if the value was greater in patients with ischemic etiology. A total of 884 patients with HFrEF (66 ± 12 years, male 73%, mean EF 28 ± 9%) underwent speckle tracking echocardiography. Of these, 61% suffered from ischemic cardiomyopathy (ICM). Patients were followed for all-cause mortality. We assessed myocardial lengthening during early systole, defined by the early systolic strain index (ESI): [-100x (peak positive strain/maximal strain)] and myocardial shortening after aortic valve closure, defined by the postsystolic strain index (PSI): [100x (postsystolic strain—peak systolic strain)/maximal strain]. During median follow-up of 3.4 [interquartile range 1.9 to 4.8] years, 132 patients (15%) died. ICM modified the relationship between ESI and all-cause mortality (P interaction = 0.008), but not for PSI (P interaction = 0.13). When assessing patients with ICM by Cox proportional hazards models, per 1% increase in ESI (HR 1.09 [1.04 to 1.15], P < 0.001) and PSI (HR 1.02 [1.01 to 1.03], P = 0.002) were associated with all-cause mortality. However, in multivariable models adjusted for clinical, invasive and echocardiographic information, only ESI was a predictor of the endpoint (HR 1.07 [1.00 to 1.13], P = 0.023). In patients with no ICM, neither ESI (HR 0.99 per 1% increase [0.90 to 1.09], P = 0.86) nor PSI (HR 1.00 per 1% increase [0.99 to 1.02], P = 0.88) were associated with all-cause mortality. Our results indicate that in HFrEF patients with ischemic etiology, the ESI may provide some information on prognosis, whereas the prognostic value of PSI is reduced. In patients with HFrEF and no prior exposure to ischemia, the prognostic value of both deformational patterns is reduced.