Background: Language and cultural differences could be a limiting factor for the international exchange of Virtual Patients (VPs), especially for small countries and languages of limited circulation. Our research evaluated whether it would be feasible to develop a VP based educational program in our Romanian institution, with cases in English and developed in a non-Romanian setting. Method: The participants in the research comprised 4th year Romanian medical students from the Faculty of Medicine in Cluj-Napoca, Romania, with previous training exclusively in Romanian, good English proficiency and no experience with VPs. The students worked on eight VPs in two identical versions, Romanian and English. The first group (2010) of 136 students worked with four VPs developed in Cluj and the second group (2011) of 144 students with four VPs originally developed at an US University. Every student was randomly assigned two different VPs, one in Romanian and another in English. Student activity throughout the case, the diagnosis, therapeutic plan and diagnosis justification were recorded. We also compared student performance on the two VPs versions, Romanian and English and the student performance on the two sets of cases, originally developed in Romania, respectively USA. Results: We found no significant differences between the students' performance on the Romanian vs. English version of VPs. Regarding the students' performance on the two sets of cases, in those originally developed in Romania, respectively in the USA, we found a number of statistically significant differences in the students' activity through the cases. There were no statistically significant differences in the students' ability to reach the correct diagnosis and therapeutic plan. Conclusion: The development of our program with VPs in English would be feasible, cost-effective and in accordance with the globalization of medical education.