AbstractIntroductionPeritoneal metastases (PM) can be treated with cytoreduction surgery (CRS) with intraoperative heated intraperitoneal chemotherapy (HIPEC) plus or minus early postoperative intraperitoneal chemotherapy (EPIC). HIPEC + EPIC may be associated with more complications than HIPEC alone.MethodsA prospective database of consecutive patients undergoing CRS + HIPEC ± EPIC at the University of Calgary between February 2000 and May 2011 was reviewed. Patient, tumor, and perioperative variables included peritoneal cancer index (PCI), completeness of cytoreduction (CCR) score, HIPEC ± EPIC type, and grade III/IV complications.Results198 patients had a CCR score of 0/1 and received: (1) HIPEC mitomycin C + EPIC 5‐fluorouracil for 5 days (n = 85; February 2000–January 2008); or (2) HIPEC oxaliplatin with IV 5‐fluorouracil + no EPIC (n = 113; February 2008–May 2011). Clinicodemographics were similar except PCI was higher in the HIPEC‐alone group (mean PCI 22 vs. 17; P = 0.02). The rate of grade III/IV complications was higher in the HIPEC + EPIC group (44.7% vs. 31.0%; P = 0.05). On multivariate logistic regression only HIPEC + EPIC and PCI > 26 were associated with an increased rate of complications.ConclusionIn patients with PM, the use of EPIC, in combination with CRS and HIPEC, is associated with an increased rate of complications. Surgeons should consider using HIPEC only (without EPIC). J. Surg. Oncol. 2013;107:591–596. © 2012 Wiley Periodicals, Inc.