Background: Muscle invasive bladder cancer (MIBC) is a chemo-sensitive disease that responds to therapy before or after curative-intent radical cystectomy (RC). Neoadjuvant chemotherapy (NAC) improves overall survival by 5-8% in current meta-analyses. Adjuvant chemotherapy (AC) has shown benefit but is less rigorously tested. Methods: We retrospectively reviewed the cystectomy database at our institute from 2005-2011 and analyzed patients who have received NAC or AC for MIBC. The Log rank test was used to compare survival between groups and Cox regression models were used for adjusted comparisons of survival. Results: 45 patients (p) (13 NAC and 32 AC) were evaluated with a mean age of 65.5 years (50-82), including 77% males and 23% females. Patients were most commonly offered chemotherapy because of co-morbidities and performance status. NAC was most commonly gemcitabine (G)/cisplatin (n=9) and AC was usually G/platinum (n=27). Sixty-nine percent of patients were downstaged and 23% had a complete pathologic response following NAC. Three p in AC group had positive margins; all of these cases were T4 cancers. Pathologic staging showed 84% ≥T3 and 53% node positive disease. Patients receiving AC had a mean interval of 64.8 days (42-129) to the start of treatment. NAC and AC patients received median 4.1 (3-7) and 4.5 cycles (1-12), respectively, throughout entire course of treatment. The median overall survival (OS) was 24.5 months (m) (17.1 m-not reached) and 24-month survival rate was 47%. Progression free survival (PFS) was 12.3 m (8.5-23.5 m) for all patients. There was no difference for OS or PFS based on age, gender, time after surgery to first dose of therapy, or mode of therapy (NAC or AC). When adjusted for number of cycles completed, a trend toward improved median OS (not reached vs. 22 m p= 0.092 ) and a significant PFS improvement (28.5 vs 11.5 m p=0.026) with NAC vs. AC was observed. Grade 3-4 urologic toxicity was negligible in both groups, however the AC group had a higher percentage of grade 3-4 hematologic toxicity. Conclusions: Despite a small sample size, results from our series favor NAC based upon efficacy and tolerability for patients with locally invasive bladder cancer.