The purpose of this study is to evaluate the relationship between LV structure and function with regional myocardial function in participants of the Multi-Ethnic Study of Atherosclerosis, which is a prospective study including 4 ethnic groups free from clinical cardiovascular disease. Peak systolic strain (Ecc) and regional strain rates (SRS and SRE) were calculated by harmonic phase from tagged CMR of 1100 participants. The relationships of ejection fraction (EF), end-systolic volume (ESV) and end-diastolic volume (EDV) with Ecc and strain rate were studied before and after adjustment for cardiovascular risk factors. Direct linear relationships between EF and regional systolic and diastolic functions (Ecc, SRS and SRE) were present in almost all of the regions (p < 0.05, i.e., greater EF, greater Ecc, SRS and SRE). LVESV demonstrated a negative relationship with Ecc and SRS (i.e., greater ESV, lower systolic function, indexed by Ecc and SRS) in all regions (p < or = 0.05). LVEDV was inversely related to systolic function, indexed by SR(S) (p < 0.05) in all regions. In conclusion, LVEF is directly related to systolic myocardial function, indexed as the absolute magnitude of systolic strain and strain rate. In addition, left ventricular size, indexed as end-diastolic and end-systolic volumes are inversely related to absolute systolic myocardial strain rate (SRS). These results are crucial to the interpretation of strain alterations induced by left ventricular remodeling in early heart failure.