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Background: In orthotopic heart transplant recipients, surveillance with endomyocardial biopsy is crucial to detect acute cellular rejection (ACR) early. ACR is a common and serious complication of transplantation with substantial morbidity and mortality. Speckle tracking echocardiography with global longitudinal strain (GLS) assessment of the left ventricle has emerged as a possible noninvasive screening modality. We have conducted a systematic literature review and meta‐analysis to evaluate the role of GLS in diagnosing ACR. Methods: The following databases were queried: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Embase. We compiled all articles evaluating changes in GLS in comparison to endomyocardial biopsy in ACR dated prior to September 2019. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled by using a random effects model. In order to determine the risk of bias, we used the revised version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool. Results: Twelve studies met inclusion criteria of which ten were chosen. These studies encompassed 511 patients and 1267 endomyocardial biopsies. There was a significant difference in GLS between patients who did and did not have ACR proven by biopsy (WMD = 2.18; 95% CI: 1.57‐2.78, P = <.001; I2 = 76%). The overall sensitivity for GLS in detecting ACR was 78% (CI: 63%‐90%, P =.123; I2 = 52.2%) while the overall specificity was 68% (CI: 50%‐83%, P = <.001; I2 = 88.3%). Conclusion: Global longitudinal strain assessment of the left ventricle by speckle tracking echocardiography is useful in detecting ACR and could potentially reduce the burden of frequent endomyocardial biopsies in heart transplant recipients. [ABSTRACT FROM AUTHOR]