In AL amyloidosis complete response (aCR) is defined as negative serum and urine immunofixation with normalized free light chain ratio (FLCR). However, achievement of low levels of involved FLC (iFLC) or difference between iFLC and uninvolved FLC (dFLC) are also relevant endpoints for treatment. We divided 434 consecutive patients with AL amyloidosis into five groups according to response 6 months after treatment initiation: aCR, iFLC <20 mg/L, normalized-iFLC, dFLC <10 mg/L, and normalized FLC ratio. Overall survival (OS) was similar (median not reached) in patients in aCR and in those who reached iFLC <20 mg/L, while it was inferior in all other groups (medians ranging from 79 to 91 months). Time to next therapy or death (TNTD) was longer in subjects attaining aCR (median 69 months) than in subjects reaching any FLC endpoint (medians ranging from 18 to 39 months). The ability of discriminating patients who survived more than 2 years among all responders was greater for current definition of aCR compared to combination of negative serum and urine immunofixation with any low-FLC endpoint. Complete response predicts best outcomes in AL amyloidosis and should be the goal of therapy if tolerability allows.