The aim of this article is to introduce and discuss prediction power of the multiple regression technique, artificial neural network (ANN), and adaptive neuro-fuzzy interface system (ANFIS) methods for predicting the forced convection heat transfer characteristics of a turbulent nanofluid flow in a pipe. Water and Al2O3 mixture is used as the nanofluid. Utilizing fluent software, numerical computations were performed with volume fraction ranging between 0.3% and 5%, particle diameter ranging between 20 and 140 nm, and Reynolds number ranging between 7000 and 21,000. Based on the computationally obtained results, a correlation is developed for the Nusselt number using the multiple regression method. Also, based on the computational fluid dynamics results, different ANN architectures with different number of neurons in the hidden layers and several training algorithms (Levenberg–Marquardt, Bayesian regularization, scaled conjugate gradient) are tested to find the best ANN architecture. In addition, ANFIS is also used to predict the Nusselt number. In the ANFIS, number of clusters, exponential factor, and membership function (MF) type are optimized. The results obtained from multiple regression correlation, ANN, and ANFIS were compared. According to the obtained results, ANFIS is a powerful tool with a R2 of 0.9987 for predictions.