Background: Neoadjuvant cisplatin-based chemotherapy for Muscle-Invasive Bladder Cancer (MIBC) is supported by level 1 evidence, however the optimal chemotherapy regimen remains to be determined. Objective: We report a five-year retrospective experience with preoperative Dose-Dense Methotrexate, Vinblastine, Doxorubicin and Cisplatin (DD-MVAC) in patients with node-negative and node-positive MIBC, with a focus on the importance of the number of chemotherapy cycles. Methods: Patients were treated between 2011 and 2015 with preoperative DD-MVAC for nodenegative or node-positive MIBC. The primary efficacy endpoint was Pathological Complete Response (pCR) on cystectomy specimens. Secondary endpoints included overall survival, relapsefree-survival and safety. Results: Sixty-nine patients were treated with DD-MVAC, among which 14 were initially nodepositive. The median number of chemotherapy cycles was 5. Fifty-five patients underwent cystectomy, of which 52% achieved pCR. Patients who received more than 4 chemotherapy cycles achieved pCR more often although this was not statistically significant (59% versus 33%, p =0.069). There were non-significant trends toward better overall survival and relapse-free survival in patients who received more than 4 chemotherapy cycles. The cumulative incidence of grade 3-4 adverse events was 62%, mainly due to hematological toxicity. Febrile neutropenia occurred in 10% of patients. No toxic death occurred. Conclusions: DD-MVAC is an effective preoperative chemotherapy regimen for MIBC, albeit responsible for frequent but manageable hematological toxicity. Pursuing chemotherapy up to 6 cycles may result in better pathological response and better survival, although this call for confirmation by larger trials.