The guinea pig has proven to be a reliable model for testing vaccine candidates against tuberculosis (TB) because of its capacity to produce human-like disease associated to primary TB, thus providing a more stringent test of the ability of a vaccine to prevent disease and deaths. Here, the BCGΔBCG1419c vaccine candidate, which previously has been shown to provide protection in mice, was tested in a guinea pig model. We found that this vaccine candidate was as effective as parental BCG in reducing M. tuberculosis H37Rv replication in lungs, and significantly reducing hematogenous spread to spleen at 60 days post-infection in comparison with BCG. Moreover, lung histopathological examination revealed comparable protection between the parental and mutant BCG strains, with some differences in prevention of primary lesions or necrosis at a single time point post-infection in a strain-dependent manner. Our results show that the BCGΔBCG1419c vaccine candidate is as effective as BCG in reducing M. tuberculosis H37Rv replication in lungs and reducing lung pathology, as well as significantly improving control of its dissemination to spleens up to 60 days post-infection.