Background: Neoadjuvant chemotherapy (NACT) with interval debulking surgery is considered for patients with advanced-stage ovarian carcinoma (OC) who are not ideal candidates for primary debulking surgery due to advanced age, frailty, poor performance status, comorbidities, or who have disease unlikely to be optimally resected. Moreover, response to NACT may be a suitable surrogate end point for long-term clinical outcome in ovarian cancer. The aim of the present study is to evaluate the utility of a three-tier Chemotherapy Response Score (CRS) and validate whether residual disease or evidence of regression following NACT may provide prognostic information in ovarian cancer. Methods: We conducted a retrospective single-institution study of patients who received NACT with carboplatin and paclitaxel for FIGO stage III/IV ovarian cancer. Response to NACT was graded as no or minimal tumor response (CRS1); appreciable tumor response amid readily identifiable viable tumor (CRS2); or complete/near-complete response with no residual tumor or minimal scattered tumor foci (CRS3) as described previously (Böhm S, et al. J Clin Oncol 33:2457-2463). Multivariate progression free survival (PFS) and overall survival (OS) analyses were performed accounting for age, FIGO stage and BRCA status. Results: Of the 86 patients accrued to date, median age was 65 years, 62% had stage IV disease and 16% had a somatic/germline BRCA mutation. CRS scores 1, 2 and 3 were found in 26 (30%), 43 (50%) and 17 (20%) of cases, respectively, and were associated with PFS (log rank p = 0.002). A high CRS score predicted improved PFS and OS (CRS 2/3 vs 1; median PFS 17.3 vs. 11.8 mo, adjusted hazard ratio (HR), 0.33; 95%CI 0.17-0.62; p < 0.001; median OS 47.9 vs. 38.3 mo, adjusted HR 0.36, 95%CI 0.15-0.88, p = 0.026). Similarly, when comparing CRS 3 with 1/2, the high score predicted improved outcome for PFS but not OS (median PFS 17.3 vs. 14.7 mo, adjusted HR, 0.42; 95%CI 0.19-0.95; p = 0.037; median OS 48.6 vs. 46.5 mo, adjusted HR 0.43, 95%CI 0.14-1.35, p = 0.149). Conclusions: In this study, we validate a simple three-tier chemotherapy response scoring system for assessing histopathologic response of OC to NACT. Residual disease and evidence of complete/near complete regression following NACT provides prognostic information in OC. CRS may serve as a potential surrogate marker for long-term outcome and be a useful alternative intermediate end point in future clinical trials.