It is well known that staging of patients with AL amyloidosis at diagnosis predicts for survival, but there is a paucity of literature delineating the prognostic value of these systems at relapse. We evaluated the prognostic value of AL staging among 413 patients initiated with second-line therapy between 2000 and 2015. Both the Revised Mayo 2012 and the European revision of Mayo 2004 staging systems were used. The median time from initial treatment to second-line therapy was 11.7 months. The first-line therapy was autologous stem cell transplant (ASCT) in 179 (43%) patients and non-ASCT therapies in 234 patients. Median survival from the institution of second-line therapy was 61 months. Both the Mayo 2004 and 2012 staging systems were of prognostic benefit at second-line therapy with respective risk ratios of 2.78 (95% CI: 2.15, 3.58) and 3.03 (95% CI: 2.33, 3.93) for patients with > stage 2 disease. On multivariate analysis, the predictive value of staging at second-line therapy was independent of stage at diagnosis and prior ASCT as first-line therapy. This study indicates that the Mayo staging systems work well at second-line therapy. Consequently, it is suitable for the stratification of patients in trials for relapsed, refractory AL amyloidosis.