BACKGROUND: Ejection fraction (EF) plays a prominent role in clinical decision making but remains dependent on image quality and left ventricular geometry. Using magnetic resonance imaging (MRI-EF) as the reference standard, we sought whether global longitudinal strain (GLS) could be an alternative to the measurement of EF. METHODS: Manual and semi-automated tracing was used to measure Simpson's biplane ejection-fraction (2D-EF) and 3D ejection fraction (3D-EF) and MRI in 62 patients with previous infarction. Global longitudinal strain was measured by 2-dimensional strain (2DS) in the apical views. Automated EF was calculated using speckle tracking to detect the end-diastolic and end-systolic endocardial border. RESULTS: Strain curves were derived in all segments, with artifactual curves being excluded. The correlation of GLS with MRI-EF (r = -0.69, P < .0001) was comparable to that between 3D-EF and MRI (r = 0.80, P < .0001), and better than that between 2D-EF (r = 0.58, P < .0001) or automated EF and MRI (r = 0.62, P < .0001). To convert GLS into an equivalent MRI-EF, linear regression was used to develop the formula EF = -4.35 (strain + 3.9). Of the 32 patients with a normal MRI-EF (> or =50%), 75% had normal systolic function by GLS, whereas 85% of patients were recognized as having a normal 3D-EF. Fewer patients were recognized as normal by 2D-EF (70%, P = .14) and automated-EF (61%, P = .04). In those with >6 abnormal segments, the correlation of GLS with MRI-EF improved significantly (r = -0.77, P < .0001) and was similar to 3D-EF (r = 0.76, P < .0001). CONCLUSION: Global longitudinal strain is an effective method for quantifying global left ventricular function, particularly in patients with extensive wall motion abnormalities.