OBJECTIVES: To assess the cost effectiveness of tapentadol PR compared with oxycodone CR for the treatment of patients with chronic severe non-cancer pain in Ireland. METHODS: A Markov model was developed to assess the costs and benefits of tapentadol PR and oxycodone CR treatment over a 1 year time horizon from the Health Service Executive perspective (GMS and DP/LTI Scheme). Patients tolerating the treatment or having mild adverse events remained on tapentadol or oxycodone. Patients who were lacking efficacy or had poor tolerability switched to either transdermal fentanyl or morphine. 3rd line therapy was defined as absorbing state. Data regarding efficacy, tolerability and utility values (EQ-5D) were derived from the 3 phase III clinical trials of tapentadol PR in osteoarthritis and lower back pain and published literature. Switch rates to 2nd line therapies and co-medication costs were provided by the National Centre of Pharmacoeconomics based on the GMS database analysis. Costs of physician visits were obtained by applying local costs to the number of physician visits in each therapy line obtained from a retrospective analysis of the UK THIN database of GP patient records. One-way deterministic and probabilistic sensitivity analyses were undertaken to assess the impact of parameter uncertainty. RESULTS: Mean annual total costs per patient from GMS Scheme perspective amount to 4,367€ for tapentadol vs. 4,381€ for oxycodone. Tapentadol generates 0.6316 QALYs compared to 0.6122 QALYs for oxycodone, resulting in tapentadol being a dominant treatment. For DP/LTI Scheme, tapentadol had an ICER of 1,662 €/QALY gained. Results were robust in a broad range of sensitivity analyses. Probability that tapentadol is cost-effective vs. oxycodone at threshold of 20,000 €/QALY gained exceeded 95%. CONCLUSIONS: Compared to oxycodone CR, the most commonly used oral drug for chronic severe non-cancer pain in Ireland, tapentadol PR appears to be a highly cost-effective treatment option.