Abstract Summary mpwR is an R package for a standardized comparison of mass spectrometry (MS)-based proteomic label-free workflows recorded by data-dependent or data-independent spectral acquisition. The user-friendly design allows easy access to compare the influence of sample preparation procedures, combinations of liquid chromatography (LC)-MS setups, as well as intra- and inter-software differences on critical performance measures across an unlimited number of analyses. mpwR supports outputs of commonly used software for bottom-up proteomics, such as ProteomeDiscoverer, Spectronaut, MaxQuant, and DIA-NN. Availability and implementation mpwR is available as an open-source R package. Release versions can be accessed on CRAN (https://CRAN.R-project.org/package=mpwR) for all major operating systems. The development version is maintained on GitHub (https://github.com/okdll/mpwR) and full documentation with examples and workflow templates is provided via the package website (https://okdll.github.io/mpwR/).