The NEQ approach for calculating ABFEs involves some parameters that are specific to this method (referred to as NEQ parameters hereafter). A systematic analysis of the effect of these parameters on the accuracy and reliability of NEQ ABFE predictions is hitherto not available. A few recent studies have used ad hoc values for NEQ parameters without providing proper justification. In this study, we have performed such a systematic analysis and discussed how each of the NEQ parameters affect predictions and make recommendations to optimise their values for ABFE calculations. We also previously reported such an analysis for NEQ RBFE calculations .