Prediction of the diameter of a nanofiber is very difficult, owing to complexity of the interactions of the parameters which have an impact on the diameter and the fact that there is no comprehensive method to predict the diameter of a nanofiber. Therefore, the aim of this study was to compare the multi-layer perceptron (MLP), radial basis function (RBF), and support vector machine (SVM) models to develop mathematical models for the diameter prediction of poly(3-caprolactone) (PCL)/gelatin (Gt) nanofibers.Four parameters, namely, the weight ratio, applied voltage, injection rate, and distance, were considered as input data. Then, a prediction of the diameter for the nanofiber model (PDNFM) was developed using data mining techniques such as MLP, RBFNN, and SVM. The PDNFM MLP is introduced as the most accurate model to predict the diameter of PCL/Gt nanofibers on the basis of costs and time-saving.According to the results of the sensitivity analysis, the value of the PCL/Gt weight ratio is the most significant input which influences PDNFM MLP in PCL/Gt electrospinning. Therefore, the PDNFM model, using a decision support system (DSS) tool can easily predict the diameter of PCL/Gt nanofibers prior to electrospinning.