Tuberculosis (TB) continues to challenge global health systems, especially in South Africa. Nurses are especially vulnerable to TB exposure, because of their prolonged front-line contact with infected patients-especially in primary health care (PHC) clinics. Their infection control practices, influenced by key factors such as knowledge and attitudes towards TB prevention, become an important consideration. The aim of the study was to (1) describe the TB prevention knowledge, attitudes, and practices of PHC nurses in a South African district and (2) explore moderating factors on TB prevention practices.