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Background Combining complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a new approach allowing curatively intended treatment of multiple malignant peritoneal tumour seedings. This aggressive treatment is frequently followed by a complicated or an unusual postoperative course, that has yet to be described. Aim To describe the clinical and biological post-therapeutic course of patients treated with CCRS plus HIPEC, who were considered uncomplicated cases, and were discharged from hospital before the 15th postoperative day. Patients and methods Thirty-two patients were retrospectively selected on these criteria among 232 treated patients, most of whom had received intraperitoneal high-dose oxaliplatin and intravenous 5-fluorouracil. The daily postoperative clinical and biological parameters are presented in graphs using boxplots. Results Hyperthermia at 38 °C was the rule during the first postoperative week. The daily flow rate of the abdominal drains decreased progressively from 500 ml to 50 ml from day 1 to day 7. The flow rate of the nasogastric tube was high and close to 1000 ml/24 h until day 6. Resumption of digestive transit occurred between day 4 and day 6; it was always a diarrheic transit until day 12. Severe hypophosphoremia was observed at day 2 and day 3. White blood cells gradually decreased until day 12 to half the normal value, haemoglobin remained stable and the platelet count, which was low after surgery, continued to decrease progressively until day 3. Other data are presented. Conclusion These results, in this selected group of patients, allow a description of the “natural history” of CCRS plus HIPEC, which is not similar to classic uncomplicated postoperative courses following surgery. Knowledge of these “natural” changes may help avoid unnecessary explorations, and allow the early detection of postoperative complications.