Background: At a medium-sized district general hospital in the heart of England, it was identified that compliance to the administration of topical prophylaxis on three general surgery wards had reduced to 23%, following implementation of an electronic medication prescription record. Therefore, a quality improvement project was commenced to improve this compliance to protect patients from meticillin-resistant Staphylococcus aureus (MRSA) colonisation and associated bacteraemia. Aim: To improve compliance of topical prophylaxis administration on three surgical wards to protect patients from infection. Method: Quality improvement plan – do – study – act (PDSA) cycles evaluated the effectiveness of four different strategies from baseline data which was 23% compliant in December 2016. These included teaching and communication strategies, prompts in medical notes, discontinuation of Mupirocin 2% nasal ointment as part of the topical prophylaxis regime and discontinuation of the topical wash lotion from requiring a prescription. Results: The compliance of prophylaxis administration increased consistently throughout from 23% in December 2016 to 92% in March 2018. Consequently, the number of patients that developed a MRSA colonisation on the three wards reduced by 54%, from 13 in the 12 months before the study to six in the 12 months after the study. Discussion: This study led to a change in the Trust MRSA Policy to better protect patients from infection, particularly surgical site infection and MRSA bacteraemia. It suggests that quality improvement methodology has a place in infection prevention practice.