Background: Despite the increasing number of studies confirming the importance of neoadjuvant chemotherapy in patients addressed to radical cystectomy (RC) for bladder cancer (BC), its association remains controversial. We aimed to test the safety and the efficacy of neoadjuvant chemotherapy in pts underwent RC for BC in a multistitutional retrospective study Methods: We analyzed 768 pts who underwent RC and PLND with / without neoadjuvant chemotherapy in two European high volume centers between 2007 and 2013. Complete demographic, pre and postoperative functional data and oncologic outcomes were collected. T-tests and Chi-square analyses were used to evaluate the differences between the groups. Kaplan-Meier curves were used to assess time to cancer specific mortality (CSM) free and overall mortality (OM) free survival. Univariable (UVA) and multivariable (MVA) logistic and Cox regression analyses were developed to address predictors of perioperative complications and CSM- and OM-free survival. Results: The mean follow up was 20 months (range 1-24). Mean age at surgery was 67 yrs (median 67 yrs). Patients had mainly pT2 disease (79,6%). Overall, 14% of pts had preoperative cisplatinum based neoadjuvant chemotherapy. We did not find any difference in pre-operative and post-operative blood tests assessment (all p>0.1). Intraoperative blood loss was higher in patients who went directly to surgery (mean 1.200 vs 740 cc; p<0.001) but the number of transfusions was similar (p=0.77) as well as the hospital stay (p=0.8). The complication rate was not significant at the MVA logistic regression analysis (p=0.74) even after evaluating per Clavien-Dindo groups (p=0.11). Neoadjuvant chemotherapy showed a better CSM-free survival at UVA (p=0.035) and at MVA (p= 0.043; OR 0.44). Then a nomogram was developed to predict the 60 months CSM-free rate showing an accuracy of 72.6%. Conclusions: Neoadjuvant chemotherapy is associated with a better CSM-free survival in patients with high-risk bladder cancer eligible for RC and it’s not linked with perioperative morbidity. We finally developed the first nomogram predicting the CSM-free rate in these patients.