In the phase 3 ANDROMEDA trial, patients treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) showed significantly higher organs hematologic response rates than those treated with VCd alone. Patient-reported outcomes (PROs) from the ANDROMEDA experiment were shown. Throughout cycle 6, 3 standardized questionnaires were used to evaluate the effectiveness of patient-reported outcomes. The treatment impact through cycle 6 was evaluated using a repeated-measures, mixed-effects model. The degree of changes in PROs relative to baseline was minor, although differences between groups benefited the D-VCd group. Results were consistent regardless of hematologic, cardiac, or renal responses. Significantly more patients in the D-VCd group exhibited improvements in PROs; the median time to improvement was shorter in the D-VCd group than in the VCd group. After cycle 6, D-VCd participants received daratumumab monotherapy, and their PRO evaluations continued until cycle 19, with improvements in health-related quality of life (HRQL) noted. The EQ-5D scores of subgroups with renal and cardiac problems were comparable to those of the total population. The outcomes supported the use of D-VCd in patients with AL amyloidosis by demonstrating that the previously observed therapeutic benefits of D-VCd were obtained without a reduction in HRQoL.