The two times-cytoreductive surgery (CRS) seems to be effective treatment because it allows complete removal of widespread masses and a reduction of surgical complications for pseudomyxoma peritonei (PMP) with high PCI. The present study verified the indication and prognostic factors of two times-CRS for patients with PMP. Between 2006 and 2017, 85(22.8%) patients were programmed a two times-surgical approach to remove the residual tumors. At 2nd CRS, complete cytoreduction (CCR-0) was done in 35(41.2%) patients. CCR-0 resection was performed significantly higher in patients with PCI ≤ 23, small bowel PCI ≤ 8 and low grade mucinous neoplasm (LAMN). Causes of incomplete cytoreduction (CCR-1) at 2nd CRS were diffuse involvement of small bowel, deep pushing invasion, massive bleeding during CRS, elderly patients older than 75 years old, and severe adhesion. Postoperative major complications after 1st and 2nd CRS were experienced in 16(18.8%) and 33(38.9%) patients, respectively. Postoperative mortality after 2nd CRS was found in 5(5.9%) patients. The 5-year overall survival of CCR-0 and CCR-1 group were 66.6% and 7.2%, respectively. CCR score and postoperative major complications after 2nd CRS were independent prognostic factors affecting overall survival. Patients with LAMN, PCI ≤ 23, and SB-PCI ≤ 8 are recommended to undergo 2nd CRS. Training of careful and gentle operation techniques are essential for the prevention of postoperative complications and survival improvement.