Background: Diabetes mellitus [DB] is a well-known risk factor for cardiovascular disease. The co-existence of DM and microvascular abnormalities could lead to hypertrophy of left ventricle [LV] with diastolic and/or systolic dysfunction. However, early stages of the disease are asymptomatic due to its chronic nature and the effective control of diabetes. Aim of the Work: This clinical cohort aimed to assess left ventricular systolic function in DM patients, receiving direct acting antiviral [DAA] drugs for chronic hepatitis-C virus by speckle tracking. Patients and Methods: This clinical cohort included 90 patients who were divided into three equal groups. Patients were recruited from Hepatology Outpatient Clinic of Kafr El-Shaikh University hospital, who were sent to the cardiovascular department for evaluation. Patients were evaluated just before, one month and three months after starting therapy.Result: No one in control group had diastolic dysfunction compared to 10.0% and 16.7% in DAAs and Non-DAAs groups, respectively. Conventional echocardiography returned statistically non-significant difference except significant increase of LVESD, IVST and LVPWT in study groups than control groups. However, the difference between DAAs and Non-DAAs groups was statistically non-significant. The basic strain parameters returned significant lower values at different windows in control than study groups. The strains were reduced in the follow up visits [first and third months] in DAAs groups, but not significantly reduced in non-DAAs group. Acute myocardial infarction was reported among one patient in non-DAAs group compared to none in DAAs group. Conclusion:The speckle tracking is a useful tool for early detection of subclinical left ventricular dysfunction in HCV diabetic patients and could be used for following up of response DAA treatment. DAAs therapy is associated with improvement, not of HCV disease, but also of cardiac dysfunction.