The present work describes a novel search program for the detection of both MS-cleavable and non-cleavable crosslinked peptides and it is the first software program reported with both capacities. The search strategy has been implemented in the computer program MetaMorpheus, which has a user-friendly graphical user interface (GUI). Novel crosslinker molecules can be easily added if desired. A fragment-ion index scheme makes the search computationally efficient. DSSO crosslinked BSA and E.coli ribosome data were used to validate the MS-cleavable crosslink search results.