Objective.: The majority of patients with advanced epithelial ovarian cancer (EOC) will experience a recurrence after primary chemotherapy and receive second-line chemotherapy. Patients who have a disease-free interval > 6 months (platinum-sensitive) will often receive multiple chemotherapy regimens. Therefore, our goal was to assess the effectiveness and medical costs of chemotherapy for platinum-sensitive patients with advanced EOC. Methods.: A decision analysis model compared several chemotherapeutic strategies in a hypothetical cohort of 10,000 platinum-sensitive EOC patients with recurrent disease: (a) best supportive care (BSC); (b) second-line monotherapy; (c) second-line combination therapy; (d) third-line chemotherapy after disease progression on second-line monotherapy or combination therapy; (e) fourth-line chemotherapy after disease progression on second- and third-line chemotherapy. Results.: BSC and second-line therapies were cost-effective strategies. The cost-effectiveness ratios ranged from $2896 for second-line monotherapy to $4914 for fourth-line previous monotherapy. Compared to BSC, second-line monotherapy gained an additional 8 months of overall survival (OS) with a favorable incremental cost-effectiveness ratio (ICER) of $24,228 per life year saved (LYS). The ICER for second-line combination therapy compared to second-line monotherapy was also favorable ($46,068 per LYS). Although third- and fourth-line chemotherapy provided small improvements in OS, they were dominated by other strategies or had an unfavorable ICER (> $50,000 per LYS). Conclusions.: Second-line chemotherapy is cost-effective for patients with platinum-sensitive recurrent EOC. Due to minimal improvements in overall survival, third- and fourth-line chemotherapy are not cost-effective strategies. © 2006 Elsevier Inc. All rights reserved.