INTRODUCTION: Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) is a treatment option for peritoneal surface malignancy. Despite the survival benefits, this treatment was previously associated with a high morbidity and mortality rates and the perception of the poor perioperative outcomes associated with this regimen remains. The aim of this study was to report the perioperative outcomes of CRS and PIC from a single institution to review factors that are associated with a poor perioperative outcome. METHODS: The clinical-and treatment-related data of 243 consecutive procedures performed were prospectively collected and retrospectively reviewed. Adverse events were rated according to the National Cancer Institute's Common Toxicity Criteria (grade I-V). Univariate and multivariate analyses were performed to identify significant clinical and treatment-related factors for a poor perioperative outcome (grades III/IV/V morbidity). RESULTS: The perioperative mortality rate was 3%. The rate of severe morbidity was 43%. Multivariate analysis demonstrated that left upper quadrant peritonectomy (P < 0.001) and small bowel resection (P < 0.01) were factors that predicted for a poor perioperative outcome. CONCLUSIONS: The morbidity and mortality rates of CRS and PIC are within an acceptable range for a major gastrointestinal surgery which is performed with a curative intent. Patient selection is important in ensuring that suitable patients receive this treatment. A new perspective of this treatment needs to be sought.