Two-stage hepatectomy with or without portal vein embolization allows treatment of multiple bilobar metastases, thereby expanding operative indications for these patients. Two operations are needed, however, and some patients are not able to complete the treatment strategy because of disease progression. Using experience gained from our policy of ultrasonographically guided resection, we explored the safety and effectiveness of 1-stage operative procedures in patients otherwise recommended for the 2-stage approach. A total of 29 patients with multiple (>or=4) bilobar colorectal liver metastases (CLM) were selected from 100 consecutive patients submitted to surgical resection. The total number of preoperative CLM was 163 (median, 5; range, 2-20). The operative strategy was based on tumor-vessel relationships at intraoperative ultrasonography (IOUS) and on findings at color Doppler IOUS. There was no in-hospital mortality. Tumor removal was feasible with 1-stage operative procedures in all but 3 patients who underwent laparotomy. The overall morbidity rate was 23% (6/26); none of the patients required reoperation. Major morbidity occurred in 1 patient (4%). Blood transfusions were administered in 4 patients (15%). After a mean follow-up of 17 months (median, 14; range, 6-54), 3 patients had died from systemic recurrence, 12 patients were alive without disease, and 11 were alive with disease. No local recurrences were observed at the resection margin. IOUS-guided resection based on strict criteria allows a 1-stage operative treatment in selected patients with multiple bilobar CLM. This strategy decreases the need for a two-stage hepatectomy, thereby avoiding the disadvantages of a 2-stage approach.