Mycobacterium tuberculosis remains a global health threat despite the world-wise use of the vaccine Bacille Calmette Guerin (BCG). Introducing a new vaccine could help to combat this pandemic, and efforts are underway to develop novel candidates, including by modifying parental BCG. Here, we use the genetically and phenotypically heterogenous Diversity Outbred mice to test the efficacy of the novel vaccine candidate BCGΔBCG1419c. BCGΔBCG1419c contains a mutation in BCG1419c, a phosphodiesterase linked with biofilm formation. BCGΔBCG1419c was previously shown to be more attenuated than the parental BCG strain in inbred mice and to provide protection against aerogenic M. tuberculosis challenge in inbred mice and guinea pigs. In the current study, we find that protection afforded by BCGΔBCG1419c in outbred DO mice is at least equivalent to, if not better than, that provided by parental BCG.