Central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) are rare. We investigated the clinico-pathological prognostic factors of patients with CNS metastases from EOC and compared the outcomes of various treatment modalities. We retrospectively reviewed the records of patients with CNS metastases from EOC between 2000 and 2020. Information on the clinical and pathological characteristics, treatment, and outcomes of these patients was retrieved from Samsung Medical Center and National Taiwan University Hospital. A total of 94 patients with CNS metastases were identified among 6,300 cases of EOC, resulting in an incidence of 1.49%. Serous histological type [hazard ratio (HR): 0.49 (95% confidence interval [CI] 0.25-0.95), p=0.03], progressive disease [HR: 2.29 (95% CI 1.16-4.54), p=0.01], CNS involvement in first disease relapse [HR: 0.36 (95% CI 0.18-0.70), p=0.002], and gamma knife radiosurgery (GKS)-based combination treatment for EOC patients with CNS lesions [HR: 0.59 (95% CI 0.44-0.79), p<0.001] significantly impacted survival after diagnosis of CNS metastases. In a subgroup analysis, superior survival was observed in patients with CNS involvement not in first tumor recurrence who underwent GKS-based combination therapeutic regimens. The survival benefit of GKS-based treatment was not significant in patients with CNS involvement in first disease relapse, but a trend for longer survival was still observed. In conclusion, GKS-based combination treatment can be considered for the treatment of EOC patients with CNS metastases. The patients with CNS involvement not in first disease relapse could significantly benefit from GKS-based combination strategies.