Background: Renal impairment (RI) is frequent complication in patients with multiple myeloma (MM). Severe RI is important prognostic factor for survival. Melphalan clearance is renal function dependent whereas cyclophosphamide is renal function independent. Therefore, it is important theme which combination regimen should be selected between melphalan-combining regimen (MPT) or cyclophosphamide-combining regimen (TCD) in elderly MM patients with RI Patients and methods: Between 2005 and 2009, 139 newly diagnosed MM patients with RI were included comparing MPT with TCD therapy as initial treatment. Sixty-two patients were given MPT regimen and 77 patients were given TCD regimen. The doses of Melphalan and cyclophosphamide were not adjusted. Results: Baseline characteristics were similar between MPT and TCD group. For determine adequate cut-off level, analysis of different cut-off levels between the 25% and 75% quartile using log-rank test determined that glomerular filtration rate (GFR), 45ml/min/1.73m2 as the cut-off point yielded the highest difference in event-free survival (EFS) and overall survival (OS). MPT subgroup with low GFR (GFR<45ml/min/1.73m2) had poorer response rates than any other subgroups. The incidence of neutropenia was higher in MPT subgroup with low GFR than others (p=0.027). Infection with febrile neutropenia was higher in MTP subgroup with low GFR. Furthermore, mortality due to the infection was higher in MPT subgroup with low GFR than others (p=0.002, Figure 2). Event-free survival (EFS) was lower in MPT subgroup with low GFR than any other groups (p<0.001). Moreover, the survival in TCD subgroup with GFR ≥ 45ml/min/1.73m2 was higher than TCD group with low GFR. Overall survival was lower in MPT subgroup with low GFR than others (p=0.001). Conclusion: In newly diagnosed elderly MM patients with RI, MPT regimen would be more toxic and less effective to RI. In contrast, TCD regimen would be effective and tolerable treatment option due to combination of cyclophosphamide independent to renal function and dexamethasone effective for RI.