We proposed the use of standard two-dimensional (2D) cine MR images with inter-slice interpolation to evaluate three-dimensional (3D) left ventricular (LV) global area strain (GAS), and investigated its clinical applicability by comparing to 2D strains. Materials and Methods: Twenty-one consecutive patients with ischemic cardiomyopathy (ICM) (63±12 years) and 12 controls without cardiac disease (68±13 years) were retrospectively enrolled. Receiver operating characteristic analysis was performed to determine the optimal cutoff of circumferential strain (CS), radial strain (RS), longitudinal strain (LS), and GAS for detection of patients with LV ejection fraction (LVEF) ≤45%. Comparison of CS, RS, LS, and GAS between controls and ICM patients was analyzed by the Wilcoxon rank-sum test. Results: The optimal cutoff of GAS has the highest diagnostic performance for detection of patients with LVEF ≤45% [area under the curve (AUC), 0.97; sensitivity, 88%; specificity, 100%] compared to the other 2D strains (CS vs. RS vs. LS; AUC, 0.85 vs. 0.85 vs. 0.73; sensitivity, 75% vs. 100% vs. 50%; specificity, 85% vs. 77% vs. 85%). LS and GAS were significantly greater for controls than ICM patients (LS:-18.6±3.2% vs.-10.1±3.2%, p<0.01, GAS:-41.3± 5.3% vs.-26.0±8.2%, p<0.01). Conclusion: GAS derived from inter-slice interpolation of 2D cine MRI is a quantitative index of 3D myocardial motion, and this technique can be applied for clinical MR examinations.