This paper describes the architecture of NewGuide, a guideline management system for handling the whole life cycle of a computerized clinical practice guideline. NewGuide components are organized in a distributed architecture: an editor to formalize guidelines, a repository to store them, an inference engine to implement guidelines instances in a multi-user environment, and a reporting system storing the guidelines logs in order to be able to completely trace any individual physician guideline-based decision process. There is a system “central level” that maintains official versions of the guidelines, and local Healthcare Organizations may download and implement them according to their needs. The architecture has been implemented using the Java 2 Enterprise Edition (J2EE) platform. Simple Object Access Protocol (SOAP) and a set of contracts are the key factors for the integration of NewGuide with healthcare legacy systems. They allow maintaining unchanged legacy user interfaces and connecting the system with whatever electronic patient record. The system functionality will be illustrated in three different contexts: homecare-based pressure ulcer prevention, acute ischemic stroke treatment and heart failure management by general practitioners.