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Purpose: To evaluate the role of radioembolization and systemic chemotherapy as a combined modality therapy for unresectable colorectal liver metastases. Patients and methods: Prospective database of a major yttrium-90 microsphere radioembolization treatment center in Sydney, Australia, that included 140 patients with unresectable colorectal liver metastases was analyzed. Tumor response, overall survival, treatment-related complications and an evaluation of its role as a combined modality therapy with systemic chemotherapy were performed. Results: One hundred and thirty-three patients (95%) had a single treatment, and seven patients (5%) had repeated treatments. Response following treatment was complete in two patients (1%), partial in 43 patients (31%), stable in 44 patients (31%), and 51 patients (37%) developed progressive disease. Combining chemotherapy with radioembolization was associated with a favorable treatment response ( P = 0.007). The median overall survival was 9 (95% CI 6.4-11.3) months with a 1-, 2-, and 3-year survival rate of 42, 22, and 20%, respectively. Primary tumor site ( P = 0.019), presence of extrahepatic disease ( P = 0.033), and a favorable treatment response ( P < 0.001) were identified as independent predictors for survival. Conclusion: Combined modality therapy appears to improve tumor response rates. Survival is influenced by tumor site, presence of extrahepatic disease, and response to therapy. Yttrium-90 microsphere radioembolization is safe and may best be combined with systemic chemotherapy for patients with unresectable colorectal liver metastases. [ABSTRACT FROM AUTHOR]