Left ventricular non-compaction (LV NC) is characterized by abnormal trabeculations that are mainly at the LV apex. Distinction between LV NC and non-specific dilated cardiomyopathies (DCMs) remains often challenging. We sought to find additive tools comparing the longitudinal strain characteristics of LVNC versus idiopathic DCM in a cohort of patients. 48 cases of LVNC (derivation cohort) were compared with 45 cases of DCM. Global and regional multi-layer (sub-endocardial, mid-wall, and sub-epicardial) LV longitudinal strain analysis was performed. Results were compared to define the best tool for distinguishing LVNC from DCM. A validation cohort (41 LVNC patients) was then used to assess the performance of the proposed diagnostic tools. In the derivation cohort, longitudinal deformation (strain) was greater in LVNC than in DCM patients. Longitudinal shortening was greater in the non-compacted segments than in the compacted ones. A mid-wall strain base-apex gradient had 88.4 % sensitivity and 66.7 % specificity in distinguishing LVNC from DCM (AUC = 0.83; cut-off of −23 or |0.23|%). In a multivariable model, the base-apex mid-wall gradient in an apical 4-chamber view was the only independent echocardiographic criteria (OR = 0.76, CI 95 % [0.66; 0.90], p = 0.0010) allowing the distinction between LVNC and DCM. In the validation cohort, the base-apex mid-wall gradient of strain had 88.4 % sensitivity, 85.7 % negative predictive values for the diagnosis of LVNC. Longitudinal strain, especially the base-apex longitudinal gradient of strain, appears as an additive valuable tool for distinguishing LVNC from DCM.