Aims: Deformation imaging, particularly of left-sided heart, is fast becoming an essential tool in clinical cardiology. However, data are scant regarding the value of biventricular and bi-atrial deformation in association with comorbidities in heart failure with reduced left ventricular ejection fraction (HFREF). Methods and Results: Forty-nine subjects (72 ± 13 years; 28 male) with HFREF and 14 age-matched controls underwent deformation imaging including LV global longitudinal strain (LVGLS%), right ventricular strain (RVS%), and left atrial reservoir strain (LARS%). Standard echo parameters included LVEF%, E/E′ ratio, and pulmonary artery systolic pressure (PASP). Mean ± SD of LVEF, LVGLS%, and RVS% were 31% ± 8%, 7% ± 3%, and 17% ± 7%, respectively, and were significantly lower compared with controls (all P <.0001). Over a follow-up period of 4.2 years, 24% of patients died and 48% had a composite outcome of death and heart failure hospitalization. In the logistic regression model, taking the composite of death and heart failure hospitalization as a dichotomous variable, RVS%, E/E′ ratio, and PASP were the only significant univariate predictors of adverse outcome (R 2  =.68, all P <.05). In the multivariate model, however, only PASP predicted adverse outcome. PASP also had the largest AUC (0.8) in the ROC analysis. A creatinine level of >88 μmol/L (SCREAT) and a cutoff value of LA reservoir strain (LARS %) at <16.7% provided the best sensitivity (86%) and specificity (40%) with an odds ratio of 3.8. In the Kaplan–Meier survival estimate, LARS%-SCREAT predicted all-cause mortality and HF hospitalization. Conclusion: Multichamber deformation imaging along with renal function and PASP could best predict adverse outcome in HFREF. © 2018 Wiley Periodicals, Inc.