OBJECTIVES: To compare costs and outcomes of alemtuzumab and chlorambucil as first line treatment for patients with high-risk (17p-) chronic lymphocytic leukemia (CLL) in the UK. METHODS: A lifetime Markov model was developed. Patients were modeled receiving treatment and moving through post-treatment response and progressive disease. Three possible lines of chemotherapy were considered, followed by final disease progression and death. Patients had CLL, were chemotherapy naïve and exhibited deletion of the chromosome 17p, a defect associated with poor prognosis and failure to respond to other CLL therapies. Response rate and duration at first line were taken from a recent randomized study, the CAM307 trial, for subsequent lines of therapy. A review of clinical literature was conducted.  Utility was estimated from a survey of the general public using a time-trade-off methodology. Costs were calculated from the perspective of the UK National Health Service. Future costs and benefits were discounted at 3.5%. RESULTS: When overall survival (OS) was assumed to be equal, treatment with alemtuzumab instead of chlorambucil increased lifetime cost per patient from £10,957 to £17,938 and increased QALYs per patient from 1.59 to 1.96 at a cost of £18,788 per QALY gained.  When OS was allowed to vary to reflect differences in progression free survival the cost per QALY fell to £14,604. Findings were most sensitive to the cost of the interventions, response rate and duration at first line.CONCLUSIONS: This study found that in the UK, the cost per QALY gained with first-line alemtuzumab therapy over chlorambucil is £18,788 in high-risk (17p-) CLL patients.