The article introduces *PRODRG*, a tool designed for high-throughput crystallography of protein–ligand complexes. *PRODRG* generates coordinates and molecular topologies suitable for X-ray refinement of protein–ligand complexes from various input formats, including existing coordinates and two-dimensional representations. The tool is tested on a subset of compounds from the Cambridge Structural Database (CSD), showing that it can produce structures with good geometries within the limits of the empirical *GROMOS87* force field. X-ray refinement using *PRODRG*-generated topologies yields results comparable to those from standard libraries, and the tool performs better with distorted starting coordinates in terms of ligand geometry and crystallographic *R* factors. The article also compares *PRODRG* with other programs like *XPLO2D/HIC-Up* and *REFMAC5/LIBCHECK*, demonstrating its reliability and efficiency in generating topologies for use in crystallographic refinement and other applications. The limitations of *PRODRG* are discussed, including its dependency on the GROMACS force field and the small number of supported elements. Future developments aim to overcome these limitations and extend the applicability of *PRODRG*.The article introduces *PRODRG*, a tool designed for high-throughput crystallography of protein–ligand complexes. *PRODRG* generates coordinates and molecular topologies suitable for X-ray refinement of protein–ligand complexes from various input formats, including existing coordinates and two-dimensional representations. The tool is tested on a subset of compounds from the Cambridge Structural Database (CSD), showing that it can produce structures with good geometries within the limits of the empirical *GROMOS87* force field. X-ray refinement using *PRODRG*-generated topologies yields results comparable to those from standard libraries, and the tool performs better with distorted starting coordinates in terms of ligand geometry and crystallographic *R* factors. The article also compares *PRODRG* with other programs like *XPLO2D/HIC-Up* and *REFMAC5/LIBCHECK*, demonstrating its reliability and efficiency in generating topologies for use in crystallographic refinement and other applications. The limitations of *PRODRG* are discussed, including its dependency on the GROMACS force field and the small number of supported elements. Future developments aim to overcome these limitations and extend the applicability of *PRODRG*.