OBJECTIVES: Argentina is one of the few countries in the region that still has a vaccination scheme of quadruple (DPT-Hib) + hepatitis B (hepB). The incorporation of a pentavalent vaccine could have an impact both in health benefits and costs. To evaluate the cost-effectiveness of incorporating a pentavalent vaccine Quinvaxem® (Berna/Novartis) vs. the current strategy. METHODS: A Markov model was built to evaluate long term costs and effects in two 750,000 newborns cohorts. Main parameters incorporated (through a international and local systematic review supplemented by local expert consensus) were: hepB incidence by age; distribution, evolution, quality of life and treatment of the of the different clinical forms; vaccine effectiveness and coverage; and costs. The base-case was from the societal perspective, and a 3% discount rate was used. Main results are expressed as costs per Quality Adjusted Life Year (QALY). RESULTS: In the DPT-Hib strategy the mean cost per person was 151.1 US$ (2006), and QALYs 29.647; while the corresponding values for the pentavalent were 82.9 US$ and 29.661 QALYs; thus 68.2 US$ would be saved per person and 0.014 QALYs would be gained. With DPT-Hib 7710 clinical HepB cases would be observed, while with pentavalent cases would be 3720, with 3990 averted episodes. Results were robust in sensitivity analysis, and also to the use of the health service perspective. CONCLUSION: A pentavalent vaccine in the national schedule would be highly cost-effective. It would not only increase health benefits, but it would also reduce societal and health services costs.