Pseudomyxoma peritonei (PMP) is a rare disease with a poor prognosis when not adequately treated. It is characterized by a complete redistribution of mucin within the peritoneal cavity. The aim of this multicentric study was to evaluate the survival, morbidity, toxicity and mortality of patients with PMP treated by cytoreductive surgery (CRS) with intraperitoneal hyperthermic perfusion (IPHP). Seventy patients with PMP (31 males and 39 females) were enrolled onto a Phase II clinical trial. One patient was operated on twice because of disease recurrence. CRS was performed with peritonectomy procedures. The closed, opened and semi-closed abdomen techniques were employed for IPHP using cisplatin plus mitomycin-C for 60 minutes under hyperthermic conditions (42.5 degrees C). Sixty two (87%) patients were optimally cytoreduced. Five-year overall survival, progression-free survival and locoregional progression-free survival were 91%, 54% and 69%, respectively. Thirteen Grade III complications occurred in 10 (14%) patients and the most frequent one was gastrointestinal fistula/perforation (11%). There was one case (1.4%) of treatment-related mortality 21 days after treatment. CRS associated with IPHP permitted complete tumour removal with an acceptable morbidity and mortality in patients with PMP. This study confirms the efficacy of the combined treatment on long-term survival and local disease control.