Mitral regurgitation (MR) promotes left ventricular (LV) dilatation and eccentric remodeling. In the presence of LV dyssynchrony and heart failure, cardiac resynchronization therapy decreases the severity of MR. Whether primary MR can cause LV dyssynchrony is unknown. We investigated whether moderate to severe primary MR causes LV dyssynchrony in the presence of LV dilation and an ejection fraction (EF) >55%. We studied 37 normal subjects and 22 patients with moderate to severe MR and no coronary artery disease. Electrocardiographically gated cine and tagged cardiac magnetic resonance imaging was performed. Two-dimensional, maximum-circumferential shortening strain and time-to-peak strain (TTPS) were computed using harmonic-phase analysis of tagged magnetic resonance imaging. LV dyssynchrony was assessed by comparing TTPS delay of various LV quadrants and TTPS dispersion among the contralateral quadrants in patients with MR and normal subjects. Statistical comparison was done using a generalized linear model for repeated measurements. LV end-diastolic and LV end-systolic volumes were significantly larger in patients with MR versus normal subjects (207 +/- 11 vs 130 +/- 4 and 73 +/- 5 vs 47 +/- 2 ml, p <0.001). LVEF did not differ in patients with MR and normal subjects. The difference in the TTPS among various quadrants and the dispersion among the contralateral quadrants of the LV myocardium was similar between patients with MR and normal subjects. In conclusion, moderate to severe MR does not cause LV dyssynchrony in patients with LV dilatation and normal LVEF. Thus, cardiac resynchronization therapy in the absence of LV dyssynchrony may not decrease the severity of MR.