South Africa (SA) is in the midst of a tuberculosis (TB) epidemic and has one of the highest TB incidence rates globally. Despite increasing global commitment to eliminate TB, SA appears to be falling behind in this regard. This article examines key challenges to effective TB infection control from a rural regional hospital perspective. It uses the Eden District in Western Cape Province as an example to share lessons learnt. This quality-improvement project identifies four priorities for improving TB infection control in George Hospital and the Eden District: (i) prioritising TB infection control in local policy; (ii) improving the quality of TB screening in the emergency centre; (iii) increasing the number of TB patients followed up; and (iv) implementing TB infection control training for all staff. This project demonstrates the role of an emergency centre in TB screening, highlighting that this should not only be a priority for primary care, but also for secondary and tertiary care. Simple interventions, such as training of local healthcare workers in TB infection control and good-quality TB screening, can initiate a behavioural change. It also stresses the importance of good communication and co-ordination of care across primary and secondary care, ensuring that patients are not lost to follow-up. Local policy needs to reflect these straightforward interventions, empowering local healthcare workers and managers to increase responsibility and accountability for TB infection control.TB is preventable, and infection control needs to become a priority throughout SA primary, secondary and tertiary care. This project highlights that simple interventions, such as engaging local healthcare workers in a co-ordinated multisystem and multidisciplinary approach, could help to reduce the number of missing TB cases and bring SA's TB epidemic under control.