Cytokine-induced killer (CIK) cells have shown cytolytic ability against ovarian cancer cells in vitro and in vivo. This study was aimed to evaluate the clinical efficacy of maintenance therapy of CIK cells in patients with advanced epithelial ovarian cancer after first-line treatment. A paired study was performed in patients with stages IIB-IV epithelial ovarian cancer after cytoreductive surgery followed by 6-8 courses of carboplatin/paclitaxel chemotherapy. A total of 92 patients who achieved complete remission after first-line treatment were enrolled in this study. Forty-six patients in the treatment group received CIK cells transfusion monthly, whereas the other 46 patients in the control group received observation with follow-up. Progression-free survival (PFS), overall survival (OS), and toxicity were evaluated. Our results showed that median PFS was 37.7 months in the treatment group and 22.2 months in the control group (P=0.004). However, although median OS in the treatment group (61.5 mo) was longer than that in the control group (55.9 mo), there was no significant difference (P=0.289). The subgroup analysis revealed that the survival advantage of PFS from immunotherapy was independent of the extent of debulking surgery and pathologic stage. After 2 courses of CIK cells transfusion, the proportion of CD4CD25CD127 regular T cells in the peripheral blood significantly decreased (P=0.006). No grades III and IV adverse reaction were found during CIK cells infusion. Maintenance therapy with CIK cells improved the PFS in patients with advanced ovarian cancer after first-line treatment with slight side effects. However, the benefits with respect to OS are still pending.