Background: Medical practice is usually performed in a context of uncertainty, where expert knowledge is used for efficiencyin the decision-making process.Objective: The aim of this study was to develop and validate a fuzzy logic-based model to predict cardiac surgery mortality risk.Methods: Four hundred and fifty patients undergoing cardiac surgery were prospectively included in the study and mortalityrisk was predicted based on five scores: 1) “clinical expert” opinion, 2) fuzzy logic-based system according to expert knowledge,3) Parsonnet, 4) Ontario and 5) EuroSCORE. The fuzzy logic model was developed in the following stages: expert selectionof different mortality predictive variables, tables of influence among variables, construction of a fuzzy cognitive map (FCM)and its implementation in an artificial neuronal network, expert-determined patient risk score, test set risk calculation basedon fuzzy predictors, validation set risk using calibrated FCM, and comparison with the other scores according to the level ofagreement and precision with ROC curves.Results: The calibrated model was used to predict the outcome of the validation set (360 patients), based on the FCM scoreand risk predicted by Parsonnet, Ontario and EuroSCORE. The ROC areas showed that FCM had at least the same performanceas other scores to predict mortality (ROC=0.793 vs. 0.775, 0.767, 0.741 and 0.701 for EuroSCORE, “expert”, Ontarioand Parsonnet, respectively).Conclusions: A fuzzy logic-based system employing expert knowledge and the implementation of an expert system is postulatedto predict cardiac surgery mortality risk. The model not only mimicked the outcomes obtained by the “expert”, but had thesame performance as others risk scores.