OBJECTIVES: In moderate postoperative pain a weak opioid in combination with a non-opioid analgesic is recommended. Corresponding fixed combinations with paracetamol include the weak opioid tramadol or codeine. The objective of this study was to determine the cost-effectiveness of the tramadol/paracetamol combination (Zaldiar®) in comparison to a codeine/paracetamol combination (with a ratio of 1:10; codeine:paracetamol) for postoperative pain after arthroscopic procedures or abdominal surgery in the Dutch health care setting. The hypothesis was that higher drug costs for the tramadol/paracetamol combination were offset by a reduction of costs associated with the treatment of side-effects. METHODS: Decision analysis was used to model the health economic outcomes. A cost-minimisation approach was appropriate since the efficacy of the two treatments proved to be the same in the dosages used. Probabilities, resource utilisation data, and unit costs were obtained from published literature, Delphi panel and official price and tariff lists (Dutch costing manual). The perspective taken was that of the health insurance. RESULTS: The study showed that six days' postoperative treatment with the tramadol/paracetamol combination is cost saving compared with codeine plus paracetamol and has fewer side-effects (costs for tramadol/paracetamol: €42.46; codeine/paracetamol: €43.56). Sensitivity analyses confirmed the robustness of the model, with the tramadol/paracetamol combination being similarly expensive or becoming the dominant strategy in 28 off 34 scenarios calculated. CONCLUSION: The results show that postoperative pain therapy with the tramadol/paracetamol combination is equally or less expensive and has fewer side effects compared with a codeine/paracetamol combination, resulting in favourable clinical and economic benefits.