RATIONALE: The HIV and TB co-epidemic has a severe impact on the South African healthcare workforce and health system. HIV- and TB- stigma directed from healthcare workers (HCWs) towards colleagues not only has a negative impact on the mental health and well-being of the HCWs, but has been identified as a barrier to their own health-seeking behaviour. It also increases the strain on the health system due to absenteeism. OBJECTIVE: This cluster-randomised trial tested an intervention to reduce HIV- and TB-stigma among HCWs. The intervention, based on the theory of Diffusion of Innovations consisted of training healthcare workers as change agents in a Social and Behavioural Change Communication workshop to help them change stigmatising attitudes in the workplace. This was supported by a social marketing campaign. METHODS: Eight hospitals in the Free State province were randomised into intervention and control group in a stratified study design. 652 respondents randomly drawn from the hospitals were surveyed on aspects of HIV and TB stigma once in 2016 and again in 2018. Since the study only used four hospitals per intervention arm, cluster-based summaries were compared when analysing the intervention effect, using the nonparametric Mann-Whitney test. To explore how the intervention worked, 24 qualitative focus groups were conducted following the intervention. RESULTS: The quantitative test did not show a significant intervention effect on stigma between intervention and control groups. Qualitative evidence reported new awareness and changed behaviour related to HIV- and TB-stigma among individual HCWs, but a combination of factors including strong social hierarchies in the workplace and the down-scaling of the original version of the intervention seemed to reduce the impact. Conclusion The findings did not indicate a significant intervention effect, but show the potential of using HCWs as change agents to reduce HIV and TB stigma in their local communities.