Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been suggested as a treatment strategy for peritoneal carcinomatosis. The objective of this data analysis was to study treatment failure after complete cytoreduction for peritoneal dissemination from appendiceal mucinous neoplasms. Before June 2006, a total of 402 patients with peritoneal dissemination from appendiceal mucinous neoplasms underwent complete cytoreduction and PIC at the Washington Cancer Institute. Patient characteristics, pathologic features, and treatment-related data were obtained from a prospective database. Survival analyses were performed by the Kaplan-Meier method and the Cox regression model. After a median follow-up of 66 months, the 5- and 10-year progression-free survival rates for these 402 patients were 70% and 67%, respectively. Disease progression was the only independent risk factor for a reduced overall survival. One hundred eleven patients (28%) developed progressive disease. Of these, 98 patients underwent second-time and 26 patients third-time CRS and PIC. Complete cytoreduction after repeat surgery was the only independent prognostic factor for improved survival. The most common sites of treatment failure were on the small bowel and in the pelvis. The present study reported the patterns of treatment failure after complete cytoreduction and demonstrated that a disease-free state is important for long-term survival in peritoneal dissemination from appendiceal mucinous neoplasms. Repeat complete cytoreduction should be pursued when possible and is associated with improved overall survival in patients with recurrent disease.