Abstract Objective To analyze the impact of secondary cytoreductive surgery (SCS) on survival outcome in a retrospective series of isolated platinum-resistant recurrent ovarian cancer. Methods We evaluate a consecutive series of 268 ovarian cancer patients with platinum-resistant relapse. Isolated recurrence was defined as the presence of a single nodule, in a single anatomic site, and was observed in 27 cases (10.1%). In all women the presence of isolated relapse was assessed at radiological evaluation, and surgically confirmed in the SCS group. Results Among the 27 patients with isolated recurrence, 16 (59.3%) received chemotherapy alone, and 11 (40.7%) complete SCS followed by non-platinum based chemotherapy. No significant differences were observed in the distribution of baseline clinico-pathological characteristics, pattern of recurrent disease, duration of PFI, and type of salvage chemotherapy between the two groups. In the SCS group, 6 patients (54.5%) showed isolated peritoneal relapse and 5 women (45.4%) showed isolated lymph nodal recurrence, and were treated with peritonectomy and lymphadenectomy, according with site of relapse. Two post-operative complications (18.2%) occurred: asymptomatic lymphocele and groin wound dehiscence. SCS significantly prolonged median time to first progression (12months vs 3months; p-value=0.016), median time to second progression (8months vs 3months; p-value=0.037), and post-relapse survival (PRS) (32months vs 8months; p-value=0.002). Residual tumor at 1st surgery (X2=5.690; p-value=0.017), duration of PFI (X2=5.401; p-value=0.020), and complete SCS (X2=4.250; p-value=0.039) retains independent prognostic role for PRS in multivariate analysis. Conclusions SCS prolongs PRS compared to chemotherapy alone in isolated platinum-resistant recurrent ovarian cancer.