OBJECTIVES: To evaluate the cost-effectiveness of bendamustine-rituximab (B-R) compared with standard of care as first-line treatment for patients with advanced indolent non-Hodgkin’s lymphoma (NHL) in England and Wales. METHODS: A patient-level simulation was adapted from the model used by the University of Sheffield School of Health and Related Research (ScHARR) in a health technology appraisal of rituximab for first-line treatment of follicular lymphoma (the most common type of indolent NHL). This approach allowed modelling of the complex treatment pathways in indolent NHL; specifically, first-line maintenance and second-line treatment choice could be modelled as a function of patient age, and prior treatment choice and outcome. Data from a Phase 3 randomised, open-label trial by the Study group indolent Lymphomas (StiL) in Germany were used to compare B-R with CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab). The relative efficacy of CHOP-R and CVP-R (cyclophosphamide, vincristine, prednisone, rituximab) was estimated as per the original ScHARR approach. The analysis was conducted from the perspective of the National Health Service, using a lifetime time horizon. One-way sensitivity and scenario analyses were conducted, including one using recently published randomised trial data comparing CVP-R with CHOP-R.  RESULTS: The base-case deterministic incremental cost-effectiveness ratio (ICER) was £5,249 per quality adjusted life year (QALY) for B-R vs. CHOP-R, and £8,092 per QALY for B-R vs. CVP-R. The alternative scenario using direct data comparing CVP-R with CHOP-R more than halved the ICER for B-R vs. CVP-R to £3,468. Owing to its better toxicity profile, B-R reduced the cost of treating adverse events by over £1,000 per patient vs. CHOP-R. None of the one-way sensitivity or scenario analyses increased the ICER above £20,000.  CONCLUSIONS: The ICERs for B-R vs. CHOP-R and CVP-R were below the thresholds normally regarded as cost-effective in England and Wales (£20,000 – 30,000 per QALY).