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A particular sub-population known to be at high risk of tuberculosis (TB) infection is health workers, with rates of infection estimated at 2–5 times that of the general population. Evidence indicates that Infection control practices are poorly implemented. The objective of this study was to investigate perceptions of knowledgeable informants regarding the macro level drivers of TB infection in the healthcare setting and explore their perceptions of barriers as well as actions that could enhance the capacities to prevent and control TB infection among HCW.This qualitative study involved semi structured interviews with 18 stakeholders working in occupational health and TB management in South Africa. These included 10 government authorities with responsibility for TB control, 4 academic experts, 2 TB advocacy group members, a legislator, and a hospital CEO. Interviews were audio recorded and transcribed verbatim, validated and analysed aided by Nvivo 11 qualitative data management software.Perceptions of the major drivers of occupationally-acquired TB that emerged from the key informant interviews included: the high incidence in the general population, budgetary constraints in healthcare system allocation, inadequate human resources dedicated to occupational health (OH), poor implementation culture, the nature of governance of OH-related issues, lack of priority for OH, and other socio-cultural factors. Improvement in the governance of TB related issues, priority setting and implementation and adherence to occupational health and safety policies were identified as crucial to improving TB prevention and control strategiesOccupational health and safety is seen as lacking in priority in the healthcare system. Although a national TB policy for HCWs will soon be launched, it is perceived that implementation and adherence to such policies remain problematic due to a chronic underfunding of the health sector in general.