Background: Cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) has improved survival in selected patients with peritoneal carcinomatosis. This study evaluates the morbidity of postoperative pancreatic fistula (PF) within the context of CRS and PIC. Methods: Two hundred seventy-one consecutive CRS and PIC procedures were evaluated. Diagnosis and classification of postoperative PF were performed according to the international study group on PF criteria. The associations between 8 clinical and 20 treatment-related factors with postoperative PF were determined by univariate and multivariate analysis. The management and clinical sequelae of postoperative PF were discussed. Results: Seventeen patients (6.3%) developed postoperative PF. None of these patients died during their in-hospital stay. Multivariate analysis identified three independent risk factors for PF: Transfusion of ≥6 units of blood (P = 0.029), operation duration of ≥9 h (P = 0.035), and splenectomy (P = 0.020). Conservative management of PF was instituted in all 17 patients and was successful in 16 (94%). The overall time to PF closure was 26 (standard deviation 16) days after diagnosis. Although PF did not contribute to procedure-related mortality, it was associated with increased length of hospital stay (P < 0.001). Conclusions: CRS and PIC presented an acceptable rate of PF that did not increase the procedure-related mortality. However, PF was associated with longer hospital stay. Most patients with PF were treated conservatively and did not require surgical intervention.