The health care systems are rapidly adopting large amounts of data, driven by record keeping, compliance and regulatory requirements, and patient care. The advances in healthcare system will rapidly enlarge the size of the health records that are accessible electronically. Concurrently, fast progress has been made in clinical analytics. For example, new techniques for analyzing large size of data and gleaning new business insights from that analysis is part of what is known as big data. Big data also hold the promise of supporting a wide range of medical and healthcare functions, including among others disease surveillance, clinical decision support and population health management. Hence, effective big data based knowledge management system is needed for monitoring of patients and identify the clinical decisions to the doctor. The chapter proposes a big data based knowledge management system to develop the clinical decisions. The proposed knowledge system is developed based on variety of databases such as Electronic Health Record (EHR), Medical Imaging Data, Unstructured Clinical Notes and Genetic Data. The proposed methodology asynchronously communicates with different data sources and produces many alternative decisions to the doctor.