Treatment of four or more colorectal liver metastases (CRLMs) is controversial and remains a relative contraindication to surgery at some institutions. We sought to assess the outcome of patients with four or more CRLMs treated with surgery. Patients (159) with four or more CRLMs were treated surgically at a single institution. The median number of treated lesions was 5 (range, 4-14). The majority of patients received neoadjuvant chemotherapy (89.9%). Forty-six (29.0%) patients underwent resection only, 12 (7.5%) underwent radiofrequency ablation (RFA) only, and 101 (63.5%) underwent resection plus RFA. The 5-year actuarial disease-free and overall survival rates were 21.5% and 50.9%, respectively. Patients who underwent RFA as part of their surgical procedure (hazard ratio [HR] = 1.81, P = 0.03) and those with a positive surgical resection margin (HR = 1.52, P = 0.01) were more likely to have a shorter time to recurrence. Patients who did not have a reduction in tumor size following neoadjuvant chemotherapy had a higher likelihood of death following surgical treatment (HR = 2.53, P = 0.01). Patients with four or more CRLMs should be considered for aggressive surgical treatment, including liver resection with or without RFA, in order to improve the chance of long-term survival. Certain clinicopathologic factors, including lack of response to neoadjuvant chemotherapy, were associated with a worse prognosis.