Background: Hepatic metastases from neuroendocrine cancer dramatically reduce survival, introducing an important opportunity for intervention. Several treatment modalities have been examined, but an optimal treatment approach has been difficult to define. We evaluated a regimen combining hepatic artery chemoinfusion with chemoembolization. Methods: Patients with neuroendocrine cancer and diffuse hepatic metastases were treated with hepatic artery chemoinfusion and chemoembolization when they demonstrated disease progression despite octreotide therapy. Four monthly cycles of 5-fluorouracil were administered via hepatic artery infusion with chemoembolization after the final 2 cycles. Response was defined by radiologic response or symptomatic improvement. Results: Seventy-seven patients were treated; 18 received chemoinfusion only. The treatment-related mortality rate was 7%. The overall response rate was 80% for patients with carcinoid or islet cell neoplasms. Median progression-free survival was 19 months. Median disease-specific survival was 39 months from the first treatment; 1- and 5-year survival rates were 78% and 27%, respectively. Conclusion: Survival after initiating this regimen was over 3 years for the majority of patients exhibiting progression of extensive, unresectable hepatic disease despite octreotide therapy. The addition of hepatic artery chemoinfusion to chemoembolization offers a high probability of clinical benefit to patients who, otherwise, have severely limited therapeutic options and a dismal survival.