ObjectiveTo compare the cost–effectiveness of three different formulations indicated for moderate and severe acute pain, commercialized in Colombia [acetaminophen500 mg + codeine 30 mg (AC), acetaminophen 500 mg + hydrocodone 5 mg (AH) andacetaminophen 325 mg + tramadol 37.5 mg (AT)]. Materials and methodsCost–effectiveness analysis using the NNT as the health outcome indicator. The costs were evaluated in two specific settings: Institutional Channel (IC), rep-resenting the cost for the Colombian Ministry of Health (SISMED 2011); Retail Channel (RC), representing consumer prices, obtained from the IMS annual average for 2011, plus an adjustment to include the average profit margin for pharmacies (10%). The incremental cost effectiveness ratios (ICER) were calculated for the three formulations and the two settings(IC and RC). The intervention values are expressed in Colombian pesos (COP). ResultsThe prices/NNT for each formulation were $1816 COP/2.2 for AC, $4772 COP/2.3 for AH and $5342/2.6 for AT. Using these data and taking AC as the comparator, the ICER for the other formulations shows the following results: in the RC, $5065 COP for AT and $19,600COP for AH; in the IC setting, $8790 COP for AT and $29,460 COP for AH. The probabilistic sensitivity analysis demonstrated that the majority of simulation results fell between the1st and 4th quadrants of the cost–effectiveness matrix, using AC as a reference. ConclusionThe analysis, from the payer and patient perspectives, demonstrates that the AC formulation has a lower cost and is more effective in reducing pain within the first 4–6 h after administration, compared with the AH and AT formulations in their specific indications.