OBJECTIVES: To evaluate the cost-effectiveness of certolizumab pegol (CZP) in the treatment of axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA), from a Greek payer perspective. METHODS: A Markov model was locally adapted to evaluate the health effects and associated costs of CZP, adalimumab (ADA), infliximab (IFX), etanercept (ETA), golimumab (GOL) and conventional care (CC) in AS; and CZP, ADA and CC in nr-axSpA. The model incorporated clinical practice patterns and the natural history of axSpA, following patients from treatment initiation to death. Efficacy data from randomized trials of comparators were included in a meta-analysis of a mixed treatment comparison analysis. The assessment period for AS and nr-axSpA was 24 and 12 weeks, respectively. Direct costs for treating axSpA (medication acquisition, administration, monitoring, and healthcare visits) and managing adverse events were considered, reflecting the year 2015. All outcomes were discounted at 3.5% annually.  RESULTS: Regarding the AS subpopulation, the total treatment cost for IFX, ADA, CZP, ETA, GOL and CC was: €67,736, €38,914, €38,721, €38,290, €35,338 and €4,110; and the quality-adjusted life years (QALYs) were: 10.031, 9.882, 9.949, 9.933, 9.903 and 9.360, respectively. CZP dominated ADA and it was cost-effective compared to ETA generating an incremental cost-effectiveness ratio (ICER) of €26,848/QALY gained (willingness-to-pay threshold: €34,000). CZP was less effective (-0.082 QALYs) but less costly (-€29,015) than IFX, whereas it was more effective (+0.046 QALYs) and more costly (+€3,383) than GOL. CZP and GOL provided the lowest ICERs versus CC amongst comparators. Regarding nr-axSpA, the total treatment cost with CC, ADA and CZP was: €4,754, €33,748 and €34,625; and QALYs were: 10.412, 10.681 and 10.948. The ICER of CZP versus CC and ADA was €55,726 and €3,289, respectively; CZP dominated ADA.  CONCLUSIONS: CZP may be considered a cost-effective option with respect to the alternative axSpA therapies in Greece.