Aim: Describe the clinical and economic burden of hospitalizations for amyloid light chain (AL) amyloidosis. Materials & methods: This retrospective analysis used nationally representative hospital discharge data (2017–2020) to report discharge status, resource use and costs for hospitalizations among patients with AL amyloidosis. Results: Of 1341 patients identified, 92% were discharged alive and 8% experienced in-hospital death. Compared with the average US hospital stay during 2017–2019 (4.7 days, mean costs of $13,046 and mean charges of $54,496), hospital stays for AL amyloidosis were longer and costlier (9.7 days, $27,098.61, $111,233.91), especially in patients with in-hospital death (12.2 days, $44,966, $182,338.18). Conclusion: AL amyloidosis is associated with significant clinical and economic burden.