Until 2004, we treated peritoneal carcinomatosis with cytoreductive surgery accompanied by perioperative systemic chemotherapy. From October 2004, we decided to initiate a hyperthermic intraperitoneal chemotherapy (HIPEC) program for this condition.To determine the effect of HIPEC on postoperative outcomes at a single institution performing a high volume of cancer operations.Sixty consecutive patients underwent cytoreductive surgery plus HIPEC (oxaliplatin; 460 mg/m2 in 2 L/m2) from October 1, 2004, through December 31, 2010. Usual perioperative factors were studied for 3 groups of patients who underwent HIPEC: 0 to 20 HIPEC procedures (period 1), 21 to 40 HIPEC procedures (period 2), and 41 to 60 HIPEC procedures (period 3).The mean peritoneal carcinomatosis index was 9.6, the mean duration of surgery was 410.7 minutes, and the mean blood loss was 450.2 mL/L. Mortality and morbidity were 0% and 33%, respectively. Grade III/IV morbidity (P = .02), transfusion (P < .01), and reintervention rate (P = .04) significantly decreased during the 3 periods. No difference was seen between the 3 periods with regard to mean peritoneal carcinomatosis index, operative duration, blood loss, mortality, overall morbidity, length of hospital stay, and readmission. The overall 1-, 3-, and 5-year survival rates of 26 patients with peritoneal carcinomatosis originating from colorectal cancer were 100%, 51%, and 37%, respectively. The overall median survival was 39 months.We observed a significant reduction of grade III/IV morbidity, perioperative transfusion, and reintervention rate after 20 procedures. The introduction of the HIPEC program was successful because of the surgical team's prior experience in cytoreductive and cancer operations.