Water trap seal loss can lead to the ingress of foul odours from the sewer network carrying harmful pathogens which can affect the health of building occupants. This loss is due to excessive negative or positive pressures within the system as a consequence of rapidly changing flow due to the unsteady nature of air and water flow discharges from appliances. This pressure regime within the system is often represented by a pressure profile along the height of the main vertical stack in the Building Drainage System (BDS). Experimental data from peer-reviewed literature and data from a unique 34-storey drainage test rig have been used as pressure profile data (Test data) for an Artificial Neural Network (ANN) model. Discharge input height (storey number) and discharge flow rate are considered to be the two independent input parameters and the pressure along the vertical stack is considered to be the output. In this work, both a Feed Forward and Back Propagation (FFBP) ANN model and a Radial Basis Function (RBF) ANN model have been used to train the algorithm. The work has confirmed the applicability of the FFBP-ANN model for steady two-phase fluid flow phenomena in BDS and allows for the prediction of pressures in a system for which no pressure data exists, by the prediction of modelled weights, based only on its physical and flow characteristics. Practical Application: Of great concern to designers of building drainage systems (BDS) is the control of pressure fluctuations within the system to prevent water trap seal loss. Prediction of a pressure profile based on the characteristics of the building – e.g. height, location of water discharge, discharge flow rate and ventilation type, would therefore increase confidence in designs, particularly in tall buildings. The work presented here addresses, for the first time, the applications of two ANN models for predicting the pressure profile in the BDS vertical stack of multi-storey buildings.