OBJECTIVES::  To evaluate the cost-utility of tapentadol prolonged release (PR) compared with oxycodone controlled release (CR) in the treatment of moderate to severe chronic pain under the perspective of the subsidized public healthcare system in Colombia. METHODS::  Two systematic reviews were performed, one including randomized controlled trials (RCTs) and another including meta-analyses. Both compared efficacy and safety of tapentadol PR with placebo or active comparators in moderate to severe chronic pain. Efficacy and safety data were selected and oxycodone CR was included as comparator. For second-line treatment, buprenorphine transdermal (TD), fentanyl TD and hydromorphone were considered. Based on published cost-utility analyses, a Markov model was developed consisting of nine health states simulating treatment lines, adverse events (AE) and discontinuations due to AE or lack of treatment effect. Time horizon was 52 weeks with weekly cycles. Transition probabilities were extracted from meta-analyses and published economic analyses. Adverse events rates were retrieved from clinical trials and meta-analyses. Mean dosage for tapentadol was obtained from an observational study, equianalgesic rates were used to obtain other drugs dosages. A 3-weeks titration was considered. Benefits were measured in quality-adjusted life-years (QALYs). A Delphi panel estimated resource use and switch rates. Direct costs were obtained from public sources; no discount rate was applied. Values were expressed in 2016 COP. One-way and probabilistic sensitivity analyses were performed. RESULTS::  Incremental QALYs of tapentadol PR versus oxycodone CR were 0.023 QALYs, resulting in incremental cost-effectiveness ratio (ICER) of COP$ 54,646,972.80. For willingness-to-pay thresholds of 1 GDP per capita (COP$24,940,164) and 3 GDP (COP$74,820,493.94), respectively 52.7% and 78.3% of tapentadol PR results were cost-effective. Most sensitive parameter was tapentadol PR 100 mg drug costs and tolerable adverse events utilities. CONCLUSIONS::  Tapentadol PR may be a cost-effective option for moderate to severe chronic pain treatment in Colombian subsidized public healthcare system.