BCG vaccine significantly reduces the risk of tuberculosis by 50% on average. Fourteen prospective trials and 12 case-control studies across populations, study designs, and TB forms show 51% protective effect.Case-control studies show 50% protective effect. Trivia and death from TB studies show 71% and 64% protection respectively.Study site latitude and validity score explain 66% variation in trial protective effect.Protection is higher for serious TB forms, possibly due to better diagnosis.Age at vaccination did not affect efficacy predictiveness. BCG vaccine efficacy persists for 50 to 60 years.Infection of mothers with schistosomiasis and filariasis influenced infant responses to neonatal BCG immunization. Heterozygosity of intron 4 (GC) and/or maternal infection with helminth parasites showed reduced efficacy of BCG vaccine against tuberculosis.BCG immunization was protective against leprosy. Evaluating the effect and safety of BCG vaccine on initially treated pulmonary tuberculosis showed BCG vaccine should help initially treated pulmonary tuberculosis patients. It would strengthen the effects of chemotherapy and reduce multidrug-resistant tuberculosis occurrence.Differences in BCG strains used in human trials may be responsible for wide range in protection levels. Investigators concluded correlations between in vitro and in vivo tests with protective efficacy in humans is difficult. Limited data from human studies suggest BCG strain used for vaccination not significant determinant of efficacy in preventing tuberculosis. Oral delivery of BCG vaccine to wildlife reservoirs of infection such as European badgers, brushtail possums, wild boar, and deer induced protection against TB. Testing of BCG vaccine in a wide range of animal species indicated it is safe and vaccination has the potential to assist in TB control in both domestic livestock and wildlife.Alternative control measures such as vaccination are urgently required. Although used in humans for nearly a century, BCG vaccine use in animals has been limited, as protection against TB has been incomplete.Valuable insights have been gained to optimise protection induced by BCG vaccine in animals and develop tests to differentiate infected from vaccinated animals.