People deprived of liberty are among the populations experiencing the highest rates of tuberculosis. Prisons typically create ideal conditions for Mycobacterium tuberculosis transmission, including overcrowding and prolonged exposure in poorly ventilated environments, and often have populations at high risk of developing disease. The development of a novel, effective tuberculosis vaccine to prevent adult pulmonary tuberculosis is considered a crucial objective for improving tuberculosis control and, ultimately, elimination. Currently, there are over a dozen vaccines in clinical development, although none of the ongoing or planned trials include people deprived of liberty. Several factors contribute to this exclusion, including historical ethical violations in medical research involving this population, as well as concerns regarding coercion and exploitation. In this Personal View, we contend that these concerns need to be weighed against people deprived of liberty’s right to participate in scientific progress and the importance of respecting their autonomy to be part of medical research. We address the key risks associated with conducting tuberculosis vaccine trials involving people deprived of liberty, propose mitigation strategies, and discuss important scientific considerations related to efficacy trials in this context.