We performed a prospective study of adjuvant hepatic arterial infusion chemotherapy after resection of colorectal liver metastases. We placed hepatic arterial infusion ports in 20 consecutive patients undergoing curative resection of colorectal liver metastases. The chemotherapy regimen was a weekly bolus of 5-fluorouracil (15 mg/kg) for 6 months. The median follow-up has been 33 months. Nine of the 18 evaluable patients (50%) have developed recurrent colorectal cancer. The liver was the only site of failure in 3 of 18 patients (17%), and extrahepatic recurrences occurred in 6 of 18 patients (33%). All patients without recurrence are alive. The median survival of the patients without recurrent disease is 39 months, compared with 27 months for those with recurrent metastatic disease (p < 0.01). In patients who received adjuvant hepatic arterial infusion chemotherapy compared with historical controls treated with surgery alone, we have observed a decreased incidence of recurrent disease after liver resection for metastases. We recommend that patients who undergo hepatic resection for colorectal metastases be considered for postoperative adjuvant chemotherapy to decrease the likelihood of recurrence and to improve survival.