Introduction: Several studies correlated the achievement of a complete response (CR) in Newly diagnosed Multiple Myeloma (NDMM) patients to long-term survival, both in young and elderly patients. We investigated the impact of age and front-line treatment on survival among CR patients. Patients and Methods: NDMM patients enrolled in 5 phase III trials were analysed. Three trials included autologous stem cell transplantation (ASCT) eligible patients: RV-MM-209 (MPR vs Mel200, followed by lenalidomide vs no maintenance), RV-MM-EMN-441 (CRD vs Mel200 followed by lenalidomide vs lenalidomide-prednisone maintenance) and HOVON65/GMMG-HD4 (PAD vs VAD, followed by bortezomib or thalidomide maintenance). Two studies enrolled elderly patients: GIMEMA-MM0305 (VMPT-VT vs VMP) and EMN01 (MPR vs CPR vs Rd, followed by lenalidomide vs lenalidomideprednisone maintenance). The primary objective was the evaluation of the impact of CR on overall survival (OS) and progression-free survival (PFS) and the relationship with age [young (ASCT-eligible) vs elderly (ASCT-ineligible) patients] and type of treatment [ASCT vs conventional chemotherapy (CC)]. Univariate analyses of OS and PFS were performed. Response was treated as time-dependent variable in a landmark analysis (at 4 months). Results: 2792 NDMM patients were retrospectively analysed; best response was available in 2646 patients. After a median follow-up of 47 months, median OS was 86 months in CR patients and 80 months in VGPR/PR patients (HR0.6, p75 years. Conclusions: CRconfirmed to be a long-term outcome predictor of OS and PFS in both young and elderly patients. ASCT induced a more profound CR with longer remission than CC. In the very elderly (>75 years) the importance ofCR should be balanced against the safety profile.