The Open Source model has got a serious momentum over last few years and has proven its benefits also in complex (especially horizontal) applications. The time of Open Source in health care is yet to come though several successful stories has been marked already. There are some specifics of Open Source in health care that are investigated in the paper. On the basis of these specifics some recommendations are proposed to reach the interoperability and integration effect. A concrete example of O3 project is presented which is promoting Open Source adoption in e-health at regional, European and World-wide levels. This project aims to give a contribution to the development of e-health through the study of Healthcare Information Systems and the contemporary proposal of new concepts, designs and solutions for the management of health data in an integrated environment: hospitals, Regional Health Information Organizations and citizens (home-care, mobile-care and ambient assisted living).