Immunoglobulin light chain (AL)-related cardiac amyloidosis (CA) has a worse prognosis than either wild type (ATTRwt) or mutant (ATTRm) transthyretin (TTR) CA. Detailed echocardiographic studies have been performed in AL, but not in TTR amyloidosis, and might give insight into this difference. We assessed cardiac structure and function and outcome in a large population of patients with CA and compared findings in TTR and AL-related disease. We analyzed 172 patients with CA (AL, n=80; ATTRm, n=36; ATTRwt, n=56) by standard echocardiography and two-dimensional speckle tracking imaging (STI)-derived left ventricular (LV) longitudinal (LS), radial (RS) and circumferential strain (CS). Despite a preserved LV ejection fraction (55±12%), LS was severely impaired in CA. Standard measures of LV function as well as STI worsened as wall thickness increased, while apical LS was preserved irrespective of the etiology of CA and the degree of wall thickening. Compared to ATTRm and AL, ATTRwt was characterized by greater LV wall thickness and lower ejection fraction. LS was more depressed in both ATTRwt and AL (respectively -11±3% and -12±4%, p=0.54), than in ATTRm (-15±4%, p<0.01 vs. AL and ATTRwt). TTR-related etiologies were favorable predictors of survival, whereas LS and advanced NYHA class were negative predictors.In patients with CA, worsening LV function correlated with increasing wall thickness regardless of etiology. Patients with ATTRwt had a statistically greater wall thickness but lesser mortality than those with AL, despite very similar degrees of longitudinal strain impairment. This paradox suggests an additional mechanism for LV dysfunction in AL amyloidosis, such as previously demonstrated light-chain toxicity.