This thesis addresses the question of how usable openEHR-aware clinical decision support can be designed and developed in order to improve the quality of health care. To answer this research question, several sub-questions were identified and investigated. This included analyzing state of the art in two different aspects of design and development and evaluation of Clinical Decision Support (CDS) and also investigating application of a customized user-centered design (UCD) process in developing openEHR-based clinical applications. Analysis of state of the art in interplay between Human-Computer Interaction (HCI) and CDS and also the intersection between CDS and Electronic Health Records (EHR) revealed that consideration of both HCI and integration of CDS into EHR is more appreciated in theory than in practice and there is still a long way to go before reaching an acceptable level in these two success factors of CDS. Moreover, the experience in designing an openEHR-based clinical application revealed that apart from benefits offered by openEHR approach, such as specifying different roles and involvement of domain experts in defining domain concepts, there are various shortcomings that need to be improved, for instance the limited support for openEHR application developers. Additionally, this study revealed that there are characteristics of the domain, tasks and users in the domain that developers should be informed about while applying UCD methods.