Fifty-eight isolates of Clostridium difficile from two distinct outbreaks were examined for inter-strain similarity by pyrolysis mass spectrometry (PMS). The first outbreak began on a geriatric acute unit and spread to a long stay geriatric facility. PMS analysis showed that most isolates from both sites were indistinguishable. Isolates obtained in the preceding year from the long stay facility were found to be closely similar to these outbreak isolates. In the second, smaller outbreak on a female medical ward in another general hospital, PMS again showed that a single strain was probably responsible. Representative isolates from these two different outbreaks were shown to be distinct. The ability to compare rapidly large numbers of isolates of C. difficile makes PMS attractive for initial screening in suspected outbreaks, providing important information for outbreak management and allowing conventional typing methods to be concentrated on relevant isolates.