Equipped with the findings from this work, we are able to provide definitive recommendations on the optimal implementation of the alchemical ABFE method in order to ensure reproducible, accurate and precise results at lowest cost. Finally, our suggested ensemble approach improves sampling while allowing one to run all the required ABFE simulations concurrently, thus minimising the wall-clock time requirements, such that the entire ABFE protocol can be run in less than two hours. This is relevant for large scale applications as thousands of ABFE predictions can be made within a few hours given sufficient resources and/or access to modern supercomputers.