Constant pH MD simulations allow for more accurate modeling of pH dependence compared to traditional MD. While a constant pH algorithm was recently implemented in the GRO-MACS MD package, 27 it has proven difficult to efficiently prepare such simulations due to the complex and error-prone nature of their setup process. Here we have presented phbuilder, a Python-based system builder tool that automates the setup process. It allows the user to set up systems for constant pH MD starting from both initial proteins and existing systems. The user can either follow the default protocol, which will generate a generally suitable setup, or provide additional details if some specific tuning is required for the system. phbuilder also allows the user to automatically set up protein titrations or parameterize new titratable groups. We expect that with the help of phbuilder, constant pH simulations will be more straightforward to set up and thereby become more readily accessible to the GROMACS user community.