The development of medical domain applications has been one of the most active research areas recently. One example of a medical domain application is a detection system for heart disease based on computer-aided diagnosis methods, where the data is obtained from some other sources and is evaluated by computer based applications. Up to now, computers have usually been used to build knowledge based clinical decision support systems which used the knowledge from medical experts, and transferring this knowledge into computer algorithms was done manually. This process is time consuming and really depends on the medical expert’s opinion, which may be subjective. To handle this problem, machine learning techniques have been developed to gain knowledge automatically from examples or raw data. Here, a weighted fuzzy rule-based clinical decision support system (CDSS) is presented for the diagnosis of heart disease, automatically obtaining the knowledge from the patient’s clinical data. The proposed clinical decision support system for risk prediction of heart patients consists of two phases, (1) automated approach for generation of weighted fuzzy rules and decision tree rules, and, (2) developing a fuzzy rule-based decision support system. In the first phase, we have used the mining technique, attribute selection and attribute weightage method to obtain the weighted fuzzy rules. Then, the fuzzy system is constructed in accordance with the weighted fuzzy rules and chosen attributes. Finally, the experimentation is carried out on the proposed system using the datasets obtained from the UCI repository and the performance of the system is compared with the neural network-based system utilizing accuracy, sensitivity and specificity.