INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) infection has increased at an alarming rate in the recent past and has major cost implications. The aim of this study is to assess the impact of a policy of pre-operative MRSA prophylaxis on the incidence of MRSA infection in patients undergoing liver resection. PATIENTS AND METHODS: A total of 585 patients underwent hepatectomy in a tertiary referral centre between January 2000 and September 2005. In September 2003, a policy of MRSA prophylaxis (nasal mupirocin and triclosan wash for 5 days) was introduced within this unit. Demographic, pathological and outcome data were compared between the pre- and post-MRSA prophylaxis cohorts. RESULTS: The prevalence of MRSA infection prior to initiating the prophylaxis protocol was 29 patients (8.3%) and this fell to 9 patients (3.8%; P = 0.029). Furthermore, patients who had MRSA-related infection had a higher incidence of additional complications compared to the rest of the cohort (P = 0.001). Total cost savings incurred as a result of this protocol over the past 2 years has been approximated at £28,893. CONCLUSIONS: Introduction of a simple MRSA prophylaxis policy has had a significant reduction on the incidence MRSA-related infection within our patient population, leading to reduced morbidity and cost saving to the UK National Health Service.