The appropriate immunization of internationally adopted children (IAC) is currently under debate and different approaches have been suggested. The aim of this study is to evaluate the clinical and economic impact of different strategies of measles, mumps, rubella, and varicella (MMRV) immunization in IAC in Italy. A decision analysis model was developed to compare three strategies: presumptive immunization, pre-vaccination serotesting and vaccination based on documentation of previous immunization. Main outcomes were the cost of strategy, number of protected IAC, and cost per child protected against MMRV. Moreover, the incremental cost-effectiveness ratio (ICER) was calculated. The strategy currently recommended in Italy (immunize based on documentation) is less expensive. On the other hand, the pre-vaccination serotesting strategy against MMRV together, improves outcomes with a minimum cost increase, compared with the presumptive immunization strategy and compared with the comparator strategy. From a cost-effectiveness point of view, vaccination based on serotesting results in being the most advantageous strategy compared to presumptive vaccination. By applying a chemiluminescent immunoassay test, the serology strategy resulted to be clinically and economically advantageous. Similar results were obtained excluding children aged <1 year for both serology methods. In conclusion, based on our analyses, considering MMRV vaccine, serotesting strategy appears to be the preferred option in IAC.