Timely and accurate detection of cardiovascular diseases (CVDs) is critically important to minimize the risk of a myocardial infarction. Relations between factors of CVDs are complex, ill-defined and nonlinear, justifying the use of artificial intelligence tools. These tools aid in predicting and classifying CVDs. In this article, we propose a methodology using machine learning (ML) approaches to predict, classify and improve the diagnostic accuracy of CVDs, including support vector regression (SVR), multivariate adaptive regression splines, the M5Tree model and neural networks for the training process. Moreover, adaptive neuro-fuzzy and statistical approaches, nearest neighbor/naive Bayes classifiers and adaptive neuro-fuzzy inference system (ANFIS) are used to predict seventeen CVD risk factors. Mixed-data transformation and classification methods are employed for categorical and continuous variables predicting CVD risk. We compare our hybrid models and existing ML techniques on a CVD real dataset collected from a hospital. A sensitivity analysis is performed to determine the influence and exhibit the essential variables with regard to CVDs, such as the patient’s age, cholesterol level and glucose level. Our results report that the proposed methodology outperformed well known statistical and ML approaches, showing their versatility and utility in CVD classification. Our investigation indicates that the prediction accuracy of ANFIS for the training process is 96.56%, followed by SVR with 91.95% prediction accuracy. Our study includes a comprehensive comparison of results obtained for the mentioned methods.