With the availability of immunomodulatory imide drugs (IMiDs) and proteasome inhibitors (PI), most patients with immunoglobulin light chain amyloidosis (AL) receive induction therapy before autologous hematopoietic stem cell transplantation (auto-HCT). In this study we evaluated the type of induction therapy and its impact on the outcome of auto-HCT in AL. We identified 128 patients with AL who underwent high-dose chemotherapy and auto-HCT at our institution between 1997 and 2013. Patients were divided into 3 groups: no induction, conventional chemotherapy (CC)-based induction (melphalan, steroids), and IMiD/PI-based induction (thalidomide, lenalidomide, or bortezomib). The hematologic response (HR) and organ response were defined according to the established criteria. Median age at auto-HCT was 58 years (range, 35 to 75). Twenty patients (15.5%) received no induction, 25 (19.5%) received CC, and 83 (65%) received IMiDs/PIs. One, 2, or 3 or more organs were involved in 90 (70%), 20 (16%), and 18 (14%) patients, respectively. After auto-HCT 12 of 20 (60%), 15 of 24 (62%), and 72 of 83 (87%) assessable patients achieved HR at 100 days in no induction, CC, and IMiD/PI groups, respectively (P = .001). Organ response at 1 year after auto-HCT was seen in 7 of 18 (39%), 14 of 24 (58%), and 37 of 79 (47%) assessable patients in no induction, CC, and IMiD/PI groups, respectively (P = .3). Achieving a hematologic complete response was associated with a significantly higher probability of achieving an organ response (P = .02). After a median follow-up of 26 months, rates of 2-year progression-free survival were 67%, 56%, and 73% in no induction, CC, and IMiD/PI groups, respectively (P = .07; hazard ratio, .5; 95% confidence interval [CI], .3 to 1.1). Rates of 2-year overall survival were 73%, 76%, and 87% in no induction, CC, and IMiD/PI groups, respectively (P = .05; hazard ratio, .4; 95% CI, .2 to .9).On multivariate analysis a low β2-microglobulin (P = .01; hazard ratio, .3; 95% CI, .1 to .7) and induction therapy with IMiD/PI (P = .01; hazard ratio, .3; 95% CI, .1 to .7) were associated with a better overall survival. Induction therapy with either CC or IMiDs/PIs is safe and feasible in selected patients with AL. IMiD/PI-based induction is associated with a longer overall survival compared with patients who received no induction or CC before auto-HCT.