This paper proposes an open and distributed clinical decision support system architecture. This technical architecture takes advantage of Electronic Health Record (EHR), data mining techniques, clinical databases, domain expert knowledge bases, available technologies and standards to provide decision-making support for healthcare professionals. The architecture will work extremely well in distributed EHR environments in which each hospital has its own local EHR, and it satisfies the compatibility, interoperability and scalability objectives of an EHR. The system will also have a set of distributed knowledge bases. Each knowledge base will be specialized in a specific domain (i.e., heart disease), and the model achieves cooperation, integration and interoperability between these knowledge bases. Moreover, the model ensures that all knowledge bases are up-to-date by connecting data mining engines to each local knowledge base. These data mining engines continuously mine EHR databases to extract the most recent knowledge, to standardize it and to add it to the knowledge bases. This framework is expected to improve the quality of healthcare, reducing medical errors and guaranteeing the safety of patients by helping clinicians to make correct, accurate, knowledgeable and timely decisions.