There are no standard renal dose adjustments for melphalan conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. The objective of this study was to evaluate the effect of melphalan dosing and chronic kidney disease (CKD) on transplant-related outcomes, progression-free survival (PFS), and overall survival (OS). A retrospective chart review was performed, and MM patients who underwent ASCT between February 2016 and September 2021 were included. Melphalan 200 mg/m2 (Mel200) or 140 mg/m2 (Mel140) was administered. The cohort was divided based on renal function: creatinine clearance (CrCl) ≥ 60 mL/min (no-CKD) and CrCl < 60 mL/min (CKD). Outcomes measured include PFS, OS, treatment-related mortality (TRM), incidence of adverse events, hospitalization duration, and hospital readmission within 30 days. Statistical analysis included Chi-square test, t-test, and Kaplan-Meier method. Logistic regression model was used to account for melphalan dose adjustment. A total of 124 patients were included (n = 108 no-CKD, and n = 16 CKD). Median age was 62 years, majority (62%) were male, and 97% had at least a partial response at time of ASCT. Of the 124 patients, nine (7%) received Mel140. Five of these patients had CKD (CrCl range: 26 - 58 mL/min), with one on hemodialysis. Median time to neutrophil engraftment was 13.6 vs. 14.9 days and median time to platelet engraftment was 18.3 vs. 18.5 days in the CKD group vs. no-CKD group, respectively (P = 0.03 and P = 0.8). When adjusting for melphalan dose reduction, the median time to neutrophil engraftment was not statistically significant (P = 0.11). At a median follow-up of 28.7 months, the median PFS for the CKD vs. no-CKD group was 60 vs. 46 months (P = 0.3). One-year OS was 93.8% in the CKD group vs. 97% in the no-CKD group. There was a higher incidence of grade 3 or 4 mucositis in the CKD group vs. no-CKD group (P = 0.013). There is no significant difference in engraftment, PFS, or OS for MM patients with CKD vs. no-CKD receiving melphalan conditioning for ASCT. Severe mucositis was significantly more common in the CKD group, including when accounting for melphalan dose reduction.