This paper evaluates the feasibility of using an Artificial Neural Network (ANN) model for estimating the nominal shear capacity of Reinforced Concrete (RC) beams against diagonal shear failure subjected to shear and flexure. A feedforward back-propagation ANN model was developed utilizing 622 experimental data points of RC beams, which include 111 deep beams data and 20 beams tested for low longitudinal steel ratios. The ANN model was trained on 70% of the data and then it was validated using the remaining 30% data (new data were not used for training). The trained ANN model was compared with three existing approaches, including the American Concrete Institute (ACI) code. The ANN model predictions when compared to the experimental data were very favorable, regarding also the other approaches. The prediction of ANN model was also checked for size effect and deep beams separately. The ANN model was found to be very robust in all situations. The safe form of ANN model was also derived and compared with the design equations of the three methods.