OBJECTIVES: To assess, from a UK NHS perspective, the cost-effectiveness of the addition of rituximab (R) to selected chemotherapies: CVP (cyclophosphamide, vincristine and prednisolone); CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and MCP (mitoxantrone, chlorambucil and prednisolone) in the first-line treatment of follicular lymphoma. METHODS: A patient level simulation model was developed with four mutually exclusive and exhaustive health states: progression free survival on first line treatment (the starting state); progression free survival on second line treatment (PFS2); progression; and death (an absorbing state). First-line treatment consisted of chemotherapy or R-chemotherapy. Patients relapsing before death move into PFS2 and are assumed to receive second-line treatment dependent on initial treatment and time of relapse. After progression, patients enter the progression state where they reside until death. The model horizon was 25 years with costs and benefits discounted at 3.5%. Separate analyses were undertaken assuming rituximab maintenance for patients who responded to R-chemotherapy in first-line induction. Evidence from phase III trial were used when possible, however due to data limitations, assumptions were necessary which increases the uncertainty in the results. RESULTS: The estimated Incremental Cost-Effectiveness Ratios (ICERs) for the addition of rituximab to CVP, CHOP and MCP were £7,720, £10,834 and £9,316 per QALY gained respectively assuming no first-line rituximab maintenance. The ICERs increased to £14,959, £21,687 and £20,493 per QALY gained respectively when maintenance treatment was assumed. The ICER was sensitive to assumptions regarding the choice of parametric distribution to model the effectiveness of first-line treatment, the maximum time a patient can remain progression-free and potential resistance to rituximab, with the most favourable (unfavourable) ICER being approximately £4,000 (£61,000) per QALY gained. CONCLUSIONS: The addition of rituximab to CVP, CHOP and MCP is expected to fall below a cost per QALY gained of £25,000 regardless of the assumption on maintenance.