Relative apical sparing of longitudinal systolic strain (LS_sys) with preserved LS_sys at apical and significantly reduced LS_sys at mid/basal segments is a typical echocardiographic feature in AL amyloidosis patients with cardiac involvement. The present study aims to evaluate the change of this typical feature over time by serial echocardiography and its impact on outcome in AL amyloidosis patients with cardiac involvement. Echocardiography was performed in 24 consecutive patients with biopsy-proven AL amyloidosis (mean age 64 ± 9 years; 50 % male) at baseline and during a median of 257 (quartiles 103–651) days follow-up. Global and segmental LS_sys were assessed by two-dimensional speckle-tracking-imaging in septal and lateral segments of the left ventricle (LV) from the apical 4-chamber view. Sixteen (67 %) patients died during a median follow-up of 487 days (quartiles 223–872). LV global and segmental LS_sys remained unchanged over time in survivors (all P > 0.05), while LV global, septal-apical and lateral-apical LS_sys significantly decreased in non-survivors. A decrease in lateral-apical LS_sys > 3.0 % independently predicted a fivefold increased all-cause mortality risk after adjustment for age, gender, NYHA class, and treatment strategies. Further, baseline serum NT-proBNP, serum albumin decrease during follow-up, baseline septal apical-to-basal LS_sys ratio and lateral-apical LS_sys decrease during follow-up remained independently predictive of increased all-cause mortality risk. Serial monitoring of serological and echocardiographic parameters is valuable to predict outcome in AL amyloidosis patients with cardiac involvement. The best follow-up parameter to predict risk for imminent death is a decrease of longitudinal systolic strain at the lateral apical segment.