Introduction: Adjuvant therapy with FOLFOX/FOLFIRI has improved resectability and consequently survival for selected patients with colorectal metastases (CRM) to the liver. The objective of this study was to determine if neoadjuvant FOLFOX/FOLFIRI was associated with increased disease-free survival (DFS) or improved overall survival (OS) in patients with CRM to the liver. Methods: All patients who underwent hepatic resection for metastatic colorectal disease during the period of 1/1/2000 to 6/31/2005 at Mayo Clinic, Rochester, MN, were reviewed (n=307). Eligible patients were divided into two groups: Group 1 (n=44) consisted of patients who received neoadjuvant FOLFOX/FOLFIRI, and Group 2 (n=55) did not receive neoadjuvant therapy. Exclusion criteria included history of hepatic arterial infusion (n=66) or other chemotherapeutic agents (n=45), documented presence of extra-hepatic metastases (n=50), upper abdominal/intraoperative radiation (n=22) history of hepatitis/cirrhosis (n=1), concomitant cancers (n=1) or a mix of the above (n=23). Kaplan-Meier Survival was used to estimate OS and DFS. Cox proportional hazards models were used to examine the association between treatment group and overall and disease-free survival. Data were adjusted for age and gender. Statistical significance was set at P<.05.Results: The cohort consisted of 58 men and 41 women. The median age was 63 years (33-90 years). The median age of patients receiving neoadjuvant chemotherapy was 58 while the median age of patients not receiving neoadjuvant therapy was 64 (p=0.03). Surgical management predominantly consisted of right hepatectomy (49%) and non-anatomic resections (40%). Patient survival for Group 1 at one, three, and five years was 93%, 62%, and 48%, respectively, with a median survival of 4.5 years. In Group 2 survival at one, three, and five years was 90%, 63%, and 45%, respectively, with a median survival of 3.7 years. There was not a significant association of treatment group with overall survival, Group 1 vs. Group 2 (HR 0.94, p =0.85). The DFS for Group 1 at 1, 3, and 5 years was 52%, 14%, and 14%, with a median DFS of 1.0 year, and the DFS for Group 2 at 1, 3, and 5 years was 52%, 24%, and 21% with a median DFS of 1.0 year. Neoadjuvant therapy is not significantly associated with improved DFS (HR=1.14, p=0.58). Conclusions: Neoadjuvant FOLFOX/FOLFIRI was employed more frequently in younger than older patients with CRM likely to increase resectability. However, neoadjuvant chemotherapy for CRM was not significantly associated with an increase in OS or DFS, and was applicable in a minority of the patients seen in our referral practice.