Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as a bacterial pathogen in patients with cystic fibrosis (CF) although its clinical effects can be variable. The aim of this study was to evaluate the efficacy of a three-step decolonization protocol for MRSA (Belfast CF MRSA decolonization protocol). Of the 17 paediatric patients treated during the five years of the study, eight (47%) were successfully decolonized following one five-day course of oral rifampicin and fusidic acid. The success rate increased to 12 (71%) patients after a second five-day oral treatment course in the 11 patients who remained culture positive at the end of the first treatment cycle. In a further four patients, clearance was achieved with a course of intravenous teicoplanin, increasing the decolonization rate to 16 of 17 patients (94%). These results compare favourably with other published studies and show that MRSA decolonization can be successful in a high proportion of paediatric CF patients.