Hepatectomy is an accepted treatment modality for large (greater than 5 cm) colorectal liver metastases (CLM). Recently, laparoscopic hepatectomy has emerged as a viable option; however, its use for patients with large CLM is undefined. A retrospective analysis of a single institution's prospective database was performed for patients with large CLM resected between 1995 and 2010. Patients were stratified by operative approach. Patient characteristics, tumor burden, operative factors, hospital course, and long-term outcomes were compared using nonparametric, Fisher's exact, and Kaplan-Meier testing. Eighty-four patients were identified. Eight patients (9.5%) underwent laparoscopic resection. Age (59.5 vs 60 years), body mass index (26.8 vs 27.5 kg/m2), size of largest tumor (6.8 vs 7.5 cm), R0 resection (100 vs 89.5%), hepatic recurrence (25 vs 43.4%), and transfusion rate (14.3 vs 30.9%) of laparoscopic compared with open resection were similar. However, complication rate (12.5 vs 60.5%; P = 0.0192), blood loss (225 vs 400 mL; P = 0.0427), and length of stay (3.5 vs 7.0 days; P = 0.0005) were significantly higher in the open resection cohort. Median disease-free survival was 14.4 and 13.2 months for laparoscopic and open patients, respectively. Laparoscopic resection appears to be a safe approach for resecting large CLM. Tumor size does not preclude laparoscopic hepatectomy.