MOTIVATION: Minimal cut sets (MCSs) for metabolic networks are sets of reactions which, if they are removed from the network, prevent a target reaction from carrying flux. To compute MCSs different methods exist, which may fail to find sufficiently many MCSs for larger genome-scale networks. RESULTS: Here we introduce irreversible minimal cut sets (iMCSs). These are MCSs that consist of irreversible reactions only. The advantage of iMCSs is that they can be computed by projecting the flux cone of the metabolic network on the set of irreversible reactions, which usually leads to a smaller cone. Using oriented matroid theory, we show how the projected cone can be computed efficiently and how this can be applied to find iMCSs even in large genome-scale networks. AVAILABILITY AND IMPLEMENTATION: Software is freely available at https://sourceforge.net/projects/irreversibleminimalcutsets/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.