In proteome studies, the application of alternative proteases, exclusively or in addition to trypsin, often increases protein sequence or proteome coverage. It has recently been shown that, in particular, the analysis of small proteins benefits from such multi-protease approaches. In the accompanying manuscript, we present a protease score that enables the objective comparison of multiple-protease digestions and a Python-based tool named CoMPaseD (Comparison of Multiple Protease Digestions), that utilises Monte-Carlo simulations to predict this score for a user-defined set of proteases and any combination of these. This tool was validated by comparing CoMPaseD-predicted protease scores with experimentally derived protease scores for Bacillus subtilis total protein extracts. While data for three proteases (trypsin, Lys-C, chymotrypsin) were obtained from the dataset with the PRIDE identifier PXD017416, this submission contains additional data for the proteases Glu-C and LysArgiNase.