PurposeTwo-dimensional (2D) strain analysis is a sensitive method for detecting myocardial dysfunction in acute cellular rejection (ACR) from post-transplant complications. This study aims to evaluate the utility of novel left (LV) and right ventricular (RV) strain parameters for prognostic risk stratification associated with ACR burden at 1-year post transplantation.Methods128 Heart transplant patients, assessed between 2012 and 2018, underwent transthoracic echocardiography and endomyocardial biopsy. 2D strain analysis was performed and history of rejection burden was assessed and grouped according to ACR burden at 1-year post transplantation. The primary endpoint was all-cause mortality at 6-years follow up.Results21 patients met primary the endpoint. Multivariate analysis of 6-year all-cause mortality showed LV global longitudinal strain (LV GLS) (Hazard Ratio [HR] = 1.21, CI = 1.06–1.49), LV early diastolic strain rate (LV ESr) (HR = 1.31, CI = 1.12–1.54), RV GLS (HR = 1.12, CI = 1.02–1.25) and RV ESr (HR = 1.26, CI = 1.12–1.47) were significant predictors of outcome. Univariate analysis also showed LV GLS, LV ESr, RV GLS and RV ESr were significant predictors of outcome. Optimal cut-off for predicting 6-year mortality for LV GLS by receive operator characteristic was 15.5% (sensitivity: 92%, specificity: 79%). Significant reductions (p < 0.05) in LV GLS, RV GLS and LV and RV ESr between rejection groups were seen.ConclusionsNon-invasive LV and RV strain parameters are predictors of mortality in post-transplant patient with ACR. LV GLS and LV ESr are superior to other strain and conventional echo parameters.