This quality improvement (QI) work was carried out in Cecilia Makiwane Hospital (CMH), a regional public hospital in the Eastern Cape, South Africa (SA). SA has among the highest incidence of tuberculosis (TB) in the world and this is a leading cause of death in SA. Nosocomial infection is an important source of TB transmission. Adherence to TB infection prevention control (IPC) measures in the medical inpatient department was suboptimal at CMH. The overall aim of this QI project was to make sustainable improvements in TB IPC. A multidisciplinary team was formed to undertake a root cause analysis and develop a strategy for change. The main barriers to adherence to IPC measures were limited knowledge of IPC methods and stigma associated with TB. Specifically, the project aimed to increase the number of: ‘airborne precaution’ signs placed above patients’ beds, patients correctly isolated and patients wearing surgical face masks. Four Plan-Do-Study-Act cycles were used. The strategy for change involved education and awareness-raising in different formats, including formal in-service training delivered to nurses and doctors, a hospital-wide TB awareness week with engaging activities and competitions, and a World TB Day provincial solidarity march. Data on adherence to the three IPC measures were collected over an 8-month period. Pre-intervention (October 2016), a mean of 2% of patients wore face masks, 22% were correctly isolated and 12% had an airborne precaution sign. Post-intervention (May 2017), the compliance improved to 17%, 50% and 25%, respectively. There was a large variation in compliance to each measure. Improvement was greatest in the number of patients correctly isolated. We learnt it is important to work with, not in parallel to, existing teams or structures during QI work. On-the-ground training of nurses and clinicians should be undertaken alongside engagement of senior staff members and managers. This improves the chance of change being adopted into hospital policy.