Background: Oxaliplatin (OX) is increasingly used for hyperthermic intraperitoneal chemotherapy (HIPC) for patients with peritoneal metastases. Our aim was to review electrolyte disturbances and complications after HIPC with oxaliplatin (OX) versus mitomycin C (MMC). Materials and Methods: We included patients enrolled in single-institution prospective clinical trials who underwent cytoreductive surgery and HIPC with MMC or OX. We reviewed patient demographics, pathology, perioperative course, HIPC administration, and postoperative electrolyte disturbances. Measured postoperative sodium values were corrected for systemic hyperglycemia using the formula: (measured Na +) × [(glucose - 100/100) × 1.6]. Results: From January 2002 to April 2009 we performed 80 HIPC procedures. A total of 60 patients (75%) received MMC (dose range 12.5-50 mg/m 2) carried in lactated ringers solution. There were 20 patients (25%) who received OX (dose range 300 × 400 mg/m 2) carried in 5% dextrose solution. For patients receiving HIPC with OX, electrolyte disturbances were the most common complication. Compared with MMC, patients receiving OX had significant 24-h postoperative uncorrected hyponatremia (P < 0.001), corrected hyponatremia (P < 0.001), hyperglycemia (P < 0.001), and metabolic acidosis (P < 0.001). In the OX group, corrected (mean 130.5) and uncorrected (mean 127.4) sodium levels were significantly lower than preoperatively (mean 139.9, P < 0.001). The overall nonelectrolyte complication rate was 56.2%. (MMC n = 33, 55.0%; OX n = 12, 60%); the 30-day mortality rate was 0% in both groups. Conclusions: Compared with MMC, HIPC with OX was associated with significant but predictable electrolyte disturbances; however, these electrolyte disturbances were not associated with higher overall complication rates. Close monitoring with early correction is imperative to maximize perioperative care. Further studies are needed to provide mechanistic insight.