Abstract Objectives. To examine the prognostic significance of Ca125 response to neoadjuvant chemotherapy and delayed primary surgical debulking in epithelial ovarian cancer patients. Methods. Retrospective chart reviews were carried out from 1997 to 2005 to identify ovarian cancer patients treated with neoadjuvant chemotherapy. Ca125 response was defined as being a decrease of at least 50% from baseline assessment. Ca125 response was assessed in two phases: prior to surgical debulking to reflect the response to neoadjuvant chemotherapy and at the end of primary chemotherapy to assess the response to debulking surgery and further chemotherapy. Cox proportional hazard models were built to model progression-free intervals using predictor variables of: age, cancer stage, tumour grade, residual disease, and Ca125 response. Results. Ninety-one patients were included. About 83% had a positive Ca125 response following three cycles of neoadjuvant chemotherapy preoperatively. Cox regressions revealed two significant predictive variables of prolonged time to first progression: younger age ( p = 0.002) and microscopic residual disease compared to suboptimal residual disease ( p = 0.003). Ca125 response to neoadjuvant chemotherapy was not significantly predictive of progression-free survivals. The estimated median survival was 71.42 months (95% CI: 44.34–78.50) in patients with > 50% Ca125 decrease from surgery and further chemotherapy whereas in those with no response, the corresponding survival estimate was 44.02 months (95% CI: 33.26–54.79). Conclusion. The lack of Ca125 response from neoadjuvant chemotherapy is not an independent prognostic factor. All patients treated with neoadjuvant chemotherapy should undergo radical debulking surgery.