This study evaluated the diagnostic role of early diastolic mitral annular velocity (E′) by tissue Doppler echocardiography for differentiating constrictive pericarditis from restrictive cardiomyopathy (primary restrictive cardiomyopathy and cardiac amyloidosis). The study group consisted of 75 patients (53 men, 22 women; mean age 62 years, range 27 to 87). Of these, 23 patients had surgically confirmed constrictive pericarditis, 38 had biopsy-proved systemic amyloidosis and typical echocardiographic features of cardiac involvement, and 14 had primary restrictive cardiomyopathy. Standard mitral inflow characteristics were measured. Tissue Doppler echocardiography was used to measure E′ at the septal annulus. E′ was significantly higher in patients with constrictive pericarditis than in those with primary restrictive cardiomyopathy or cardiac amyloidosis (12.3 vs 5.1 cm/second, p <0.001). An E′ cut-off value ≥8 cm/second resulted in 95% sensitivity and 96% specificity for the diagnosis of constrictive pericarditis. There was no overlap of E′ between patients who had constrictive pericarditis and those who had cardiac amyloidosis. In a subgroup analysis of restrictive cardiomyopathy, E′ of patients who had cardiac amyloidosis was significantly lower than that of patients who had primary restrictive cardiomyopathy (4.6 vs 6.3 cm/second, p <0.001). Thus, E′ velocity can distinguish between constrictive pericarditis and restrictive cardiomyopathy with a specific cut-off value in patients with clinical and echocardiographic evidence of diastolic heart failure.