Aims Functional mitral regurgitation (MR) is prevalent among patients with left ventricular (LV) dysfunction and is associated with a poorer prognosis. Our aim was to assess the primary determinants of MR severity in patients with ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM). Methods and Results Patients with functional MR secondary to ICM (n = 55) and DCM (n = 48) were prospectively enrolled. Effective regurgitant orifice (ERO) area, global LV remodeling, regional wall-motion abnormalities, and mitral apparatus deformity indices were assessed utilizing conventional and tissue Doppler echocardiography. ICM patients had more severe MR compared with DCM patients despite similar ejection fraction and functional status (ERO = 0.16 ± 0.08 cm2 vs. ERO = 0.12 ± 0.70 cm2, respectively, P = 0.002). Regional myocardial systolic velocities in mid-inferior and mid-lateral wall were negatively correlated with ERO in ICM and DCM patients, respectively. Multivariate analysis identified coaptation height as the only independent determinant of ERO in both groups. In a subset of ICM patients (n = 9) with relatively high ERO despite low coaptation height, a higher prevalence of left bundle branch block was detected (88.9% vs. 46.7%, P = 0.02). Conclusions Functional MR severity was chiefly determined by the extent of mitral apparatus deformity, and coaptation height can provide a rapid estimation of MR severity in heart failure patients. Additional contributory mechanisms in ICM patients include depressed myocardial systolic velocities in posteromedial papillary muscle attaching site and evidence of global LV dyssynchrony. © 2013, Wiley Periodicals, Inc.