Embodiments of the invention provide a system, method and computer program product for reducing the hold-up volume of a pump. More particularly, embodiments of the invention can determine, prior to dispensing a fluid, a position for a diaphragm in a chamber to reduce a hold-up volume at a dispense pump and/or a feed pump. This variable home position of the diaphragm can be determined based on a set of factors affecting a dispense operation. Example factors may include a dispense volume and an error volume. The home position for the diaphragm can be selected such that the volume of the chamber at the dispense pump and/or feed pump contains sufficient fluid to perform the various steps of a dispense cycle while minimizing the hold-up volume. Additionally, the home position of the diaphragm can be selected to optimize the effective range of positive displacement.