OBJECTIVE: The authors assessed the impact of gastrinoma resection on the subsequent development of hepatic metastases in Zollinger-Ellison syndrome. SUMMARY BACKGROUND DATA: The symptoms of acid hypersecretion can be controlled medically in Zollinger-Ellison syndrome with high-dose pharmacologic therapy. The current role of surgery is curative excision of the gastrinoma. Because biochemical cure is obtained only in a portion of the patients and the neoplastic disease may be indolent in this syndrome, the ability of surgical resection of gastrinoma to alter or improve the subsequent development of hepatic metastases and mortality has not been defined. METHODS: One hundred twenty-four patients with the biochemical diagnosis of Zollinger-Ellison syndrome and no hepatic metastases on initial imaging studies were evaluated. Ninety-eight patients underwent surgical exploration for curative gastrinoma resections while 26 patients were managed medically. Long-term follow-up regarding development of hepatic metastases and survival were evaluated. RESULTS: Surgical exploration with gastrinoma excision resulted in a significantly decreased incidence of hepatic metastases 3% (3/98) compared with patients managed medically 23% (6/26) with comparable follow-up (p < 0.003). Two deaths due to metastatic gastrinoma occurred in the nonoperative group compared with no disease-specific deaths in the surgical group (p = 0.085). CONCLUSIONS: For the patient with Zollinger-Ellison syndrome without metastatic disease, surgical exploration with attempted curative gastrinoma resection is recommended because it may alter the natural history of this syndrome.