OBJECTIVES: To evaluate the cost-effectiveness of certolizumab pegol (CZP) either as an add-on therapy to methotrexate (MTX) or as monotherapy versus other biological DMARDs, in the treatment of patients with active RA who did not respond adequately to DMARDs, including MTX, in the United Kingdom (UK). METHODS: A cost-utility model with a Markov structure was developed following BSR and NICE guidelines. Comparators considered in the analysis were licensed and recommended TNF-α inhibitors in England and Wales (etanercept [ETA], adalimumab [ADA] and infliximab [IFX]), + MTX or as monotherapy (ETA and ADA only). Clinical efficacy, history and resource use data came from published literature. Unit costs were taken from routine sources/published references. Utilities were derived from EQ-5D data collected in CZP RA clinical trials. Cost for CZP assumed the first 12 weeks free of charge, as per the patient access scheme. Base case analysis was conducted from the NHS perspective, with lifetime horizon, costs and outcomes discounting rates of 3.5%. Sensitivity analyses were conducted. RESULTS: Base case analysis indicated that CZP is cost-effective compared with all combination and monotherapies considered. CZP+MTX dominated the comparators considered. CZP+MTX was associated with an incremental gain in quality-adjusted life years (QALYs) of 0.242, 0.065 and 0.458 when compared with ADA+MTX, ETA+MTX and IFX+MTX, respectively. Total costs for CZP+MTX were lower than comparator combination therapies by £451, £582 and £10,016, respectively. CZP+MTX had the highest probability of being cost-effective of the TNF inhibitor + MTX therapies considered (at £20,000/QALY, 53.6% for CZP+MTX, 25% for ETA+MTX, 21.2% for ADA+MTX, 0.2% for IFX+MTX). Among monotherapies, CZP dominated ADA (QALY incremental gain: 0.215, total costs lower by £2,352 vs ADA). CZP was cost-effective below a willing-to-pay threshold of £31,582/QALYs vs ETA.  CONCLUSIONS:  This analysis indicates that CZP is a cost-effective treatment for RA in the UK.