Here a workflow is proposed for the improved identification of proteolytic cleavage products using firstly a combination of peptide mass search engines that maximizes the number of positively identified spectra corresponding to a cleavage event. Then, the output is combined and used for running a subsequent spectrum library search for the detection of possible post-translational modifications. Using this workflow we identified 3,804 unique peptides and 5,935 spectra corresponding to 107 additional Matrix Metalloproteinase (MMP) 2 cleavage substrates, 5 neo N-termini generated exclusively by MMP-9, and 27 substrates shared by both MMP-2 and MMP-9. Additionally, we identified amino acids (AA) at the cleavage sites prone to missed cleavage or addition; all of which were not previously reported in a prior publication from which the initial data was derived. Implementing this workflow overcomes the issues one may face whilst combining results obtained from multiple sequence database search tools and creating spectrum libraries.