Background: New tuberculosis (TB) vaccines are required to meet global targets for TB control. Objectives: To determine willingness to participate (WTP) in new TB vaccine trials, willingness to be vaccinated with a newly licensed TB vaccine and associated factors among human immunodeficiency virus (HIV) infected persons. Setting: Two primary care clinics in South Africa. Design: Cross-sectional study design. Participants were asked about WTP and willingness to be vaccinated. Demographic, clinical, knowledge of TB and perception of risk information were collected. Log binomial regression was used to determine associated factors. Results: A total of 827 participants were included in the analysis: 80.4% female, 72.2% on antiretroviral therapy, median age 35 years (interquartile range [IQR] 2942 years), CD4 count 523 cells/mu l (IQR 427-659 cells/mu l). WTP and willingness to be vaccinated were high, at 84.5% and 92.6%, respectively. WTP was associated with knowledge about TB (prevalence ratio [PR] 1.10, 95% confidence interval [CI] 1.03-1.17) and perception of risk (PR 1.07, 95% CI 1.01-1.13). Willingness to be vaccinated was associated with employment (PR 1.04, 95% CI 1.01-1.08) and perception of risk (PR 1.05, 95% CI 1.01-1.09). Conclusions: There was high WTP in TB vaccine trials and willingness to be vaccinated among HIV-infected patients with good TB knowledge and high perceived risk of contracting TB.