OBJECTIVES: Cetuximab in combination with irinotecan (cet/iri) is a new chemotherapy option for patients with EGFR-expressing metastatic colorectal cancer after failure of irinotecan-including cytotoxic therapy. In Scotland, the prognosis for patients with metastatic colorectal cancer (mCRC) is poor and there are limited therapy options after the failure of conventional cytotoxic agents. Our objective was to determine the incremental cost-effectiveness of cet/iri compared to current practice in Scotland. METHODS: Given there are no licensed treatment options for this patient group in Scotland, the economic evaluation compared cet/iri with best/active supportive care (ASC). The perspective of the economic evaluation was that of the National Health Service in Scotland. The economic evaluation was based on a pivotal clinical trial comparing cetuximab in combination with irinotecan with cetuximab monotherapy (BOND). As the BOND study did not directly compare cet/iri with ASC, the data were ‘bridged' to estimate overall survival. Sensitivity analyses are presented by way of both probabilistic analysis and univariate sensitivity analysis. RESULTS: Data from the BOND study showed median time to disease progression (TTP) is significantly longer with cet/iri, 4.1 months, than cetuximab alone, 1.5 months. Median survival was 8.6 months for cet/iri and 6.9 months for cetuximab. In our evaluation, estimated mean overall survival was 10.8 months for cet/iri and 5.6 months for ASC. Over the duration of the economic model, cet/iri patients incurred additional costs of £13,851 and gained additional 0.42 life-years per patient compared with ASC patients. The incremental cost per life-year gained for cet/iri versus ASC was £32,752. The incremental cost per QALY gained was £34,454. CONCLUSIONS: Cet/iri is an effective chemotherapy option for mCRC patients failing conventional cytotoxic agents and who have limited therapy options. Our study shows that cet/iri is also within the range of acceptable cost-effectiveness when compared to other oncology therapies.