Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPC) is a promising treatment for patients with peritoneal malignancies. Traditionally, HIPC is performed concurrently with cytoreductive surgery. However, this strategy is associated with significant morbidity and mortality. In this report, we describe our initial experience with staged laparoscopic infusion of HIPC. Five patients underwent complete open cytoreductive surgery followed by staged laparoscopic HIPC several weeks later. Primary malignancies included adenocarcinoma of the ileum (one patient), adenocarcinoma of the appendix (three patients), and adenocarcinoma of the gallbladder (one patient). At a subsequent operation, we performed laparoscopic HIPC. Quality of life was measured with the Functional Assessment of Cancer Therapy-Colon Subscale (FACT-C). Mean inflow and outflow cannula temperatures were 42.1° C and 40.5° C, respectively. Mean peritoneal perfusion flow rates were 689.8 ml/minute. The hospital stay for all patients was 1 to 2 days. One patient developed postoperative cellulitis, one patient died of progressive tumor, and four patients are alive without tumor progression. Quality-of-life measurements had returned to baseline 4 months after treatment. Staged laparoscopic HIPC after open cytoreductive surgery is safe, feasible, and can achieve uniform temperatures and perfusion flow rates. Although the results of this pilot study are encouraging, additional studies are required to determine long-term survival and quality of life.