Objective: To determine if the timing of normalization of CA-125 levels during primary chemotherapy for epithelial ovarian cancer (EOC) could predict survival. Methods: Patients who reached a complete clinical response for EOC with primary taxane/platinum-based chemotherapy were eligible. Patient demographics, chemotherapy administration, CA-125 levels, and survival outcomes were abstracted. Progression free survival (PFS), overall survival (OS), and platinum sensitivity (> 6 months from chemotherapy completion) were compared to CA-125 levels during primary therapy. Results: 262 patients who achieved a complete clinical response were identified. Patients who achieved normalization of CA-125 by 3rd cycle of chemotherapy were compared to patients who failed to achieve normalization by the 3rd cycle. Patients with early normalization demonstrated improved PFS (19 vs. 6 months; p < 0.001), OS (48 vs. 27 months; p < 0.001) and platinum sensitivity (78 vs. 22%; p < 0.001). This survival advantage was maintained when patients were evaluated by debulking status. Additionally, when stratified by the specific cycle patients' achieved normalization, PFS ranged from 25 months after surgery to 2 months after 6th cycle (p < 0.001). OS demonstrated a similar trend from 74 months to 22 months (p < 0.001), while platinum sensitivity decreased from 72% to 24% (p < 0.001). An average of 3.8 months in PFS and 8.6 months of OS was gained for each one-cycle improvement in CA-125 normalization. Conclusion: Earlier normalization of CA-125 levels during primary chemotherapy for EOC predicts improvement in platinum sensitivity, PFS, and OS. This data provides prognostic information that may influence future decisions regarding chemotherapy and potentially earlier enrollment in treatment protocols. © 2009 Elsevier Inc. All rights reserved.