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• Artificial Intelligence to predict two-phase frictional pressure gradient. • Collection of a pressure drop database for a wide range of operating conditions. • Effect of the output and input type and numerosity on prediction accuracy. • Good accuracy with non-dimensional output and mixed input values. • Conventional methods always preserve physical trend with respect to neural networks. This paper presents a discussion on several possibilities to predict the frictional pressure gradient during two-phase flow, with both the application of artificial intelligence and the implementation of conventional correlations and predictive methods. To this purpose, a huge database of approximately 8000 data points has been collected from 49 sources available in scientific literature, including 23 working fluids and the following ranges of parameters: mass fluxes from 32.7 to 2000 kg/m2s, saturation temperatures from -190°C to +120°C (reduced pressures from 0.021 to 0.780), tube diameters from 0.5 to 14.0 mm. This consolidated database has been used to train several artificial neural networks (ANNs), by using only two hidden layers (shallow neural networks) and evaluating the effect of: training and testing datasets choice (either test data included or outside the training domain), the number of neurons for each hidden layer (from 1 to 50), the type of output (either dimensional or non-dimensional), the type and number (from 1 to 22) of input parameters. The best results (MAPE of 16.8% and 88% of data within ±30%) have been obtained by using the liquid-only two-phase multiplier Φ L O 2 as non-dimensional output and 12 mixed input parameters. Compared to the statistics of well-established literature correlations for frictional pressure drop (best MAPE of 22% and 73% of data points predicted within a ±30% error range, provided by Mauro et al. mechanistic method), the ANN demonstrates therefore a higher general accuracy. However, the use of Artificial Neural Networks does not guarantee a physical trend, which is instead preserved with conventional prediction methods. [ABSTRACT FROM AUTHOR]