Fear of stigma and discrimination among health care workers (HCWs) in South African hospitals is thought to be a major factor in the high rates of HIV and tuberculosis infection experienced in the health care workforce. The aim of the current study is to inform the development of a stigma reduction intervention in the context of a large multicomponent trial. We analysed relevant results of four feasibility studies conducted in the lead up to the trial. Our findings suggest that a stigma reduction campaign must address community and structural level drivers of stigma, in addition to individual level concerns, through a participatory and iterative approach. Importantly, stigma reduction must not only be embedded in the institutional management of HCWs but also be attentive to the localised needs of HCWs themselves.