A Brazilian study compared the diagnostic accuracy and safety of the Diaskintest with the tuberculin skin test (TST) in adults vaccinated with the BCG vaccine. The study included 136 tuberculosis patients and 337 healthy controls and was conducted from July 2023 to September 2024 in eight Brazilian centers. The TST showed a higher sensitivity for detecting tuberculosis (84%) compared to the Diaskintest (68%), but the Diaskintest showed a higher specificity (93% versus 75%). Adverse injection site reactions occurred less frequently with Diaskintest (1.7%) than with TST (4.9%), with phyctenular reactions and pruritus being the most common. No serious adverse events were observed in either trial. The results suggest that test selection should take into account programmatic priorities and the local epidemiological context, as each test has a different ratio between sensitivity and specificity.