Background: The optimal perioperative chemotherapy for patients (pts) with muscle-invasive bladder cancer remains open to discussion. The primary endpoint of the VESPER trial (NCT 018 12369)was previously reported with dd-MVAC improved-3 years PFS over GC schedule. In the neoadjuvant group, a better bladder local control and significant difference on 3y-PFS was observed in the dd-MVAC arm (p=0.025). Patients and Methods: Between February 2013 and February 2018, 500 pts were randomized in 28 French centers and received either 4 cycles of GC every 3 weeks or 6 cycles of dd-MVAC every 2 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). We report the final analysis of the VESPER phase III trial with the overall survival (OS) data after 5 years of follow-up from randomization. Results: 437 pts (88%) received neoadjuvant chemotherapy, 60% of patients received the planned 6 cycles in the dd-MVAC arm, 84% received 4 cycles in the GC arm, thereafter 91% and 90% of patients underwent surgery, respectively. Final median of follow-up was 5 years and 3 months and 190 deaths were reported within 5 years of follow-up. OS at 5 years was improved in the dd-MVAC arm (64% vs 56%, HR=0.77 (95% CI, 0.58-1.03), p=0.078), as was also disease-specific survival (DSS) (5-year rate: 72% vs 59%, HR=0.63 (95% CI, 0.46-0.86), p=0.004). The main cause of death was bladder cancer progression (83%), other causes included cardio-vascular events (4.2%), toxic deaths (2.1%), second cancers (2.1%), others (4.7%) and undocumented deaths (4.2%). In the neoadjuvant group, OS was significantly superior in the dd-MVAC arm (5-year rate: 66% vs 57%, HR=0.71 (95% CI, 0.52-0.97), p=0.032) as well as DSS (5-year rate: 75% vs 60%, HR=0.56 (95% CI, 0.39-0.80), p=0.001). In the adjuvant group, the results were not conclusive due to the limited sample size (n=56). Conclusions: Dose-dense MVAC provided a better OS at 5 years and improved significantly DSS over GC in the peri-operative setting of MIBC. Clinical trial information: NCT01812369.