OBJECTIVE: To investigate the extent to which relapse and other previously treated tuberculosis (TB) contribute to the notified TB burden in South Africa.DESIGN: We conducted an ecological analysis at the level of the 52 South African health districts using national electronic TB register data. We included all bacteriologically confirmed TB cases treated for presumed drug-susceptible TB in 2011. Treatment history information was based on recorded patient categories (new vs. retreatment).RESULTS: Relapse and other previously treated TB cases constituted between 7.6% and 40% (median 17%, interquartile range 12-22) of all bacteriologically confirmed TB cases in the 52 South African districts. Multivariable analysis suggested that districts with higher proportions of previously treated TB cases had higher TB case notification rates (P < 0.001), lower estimates of antenatal human immunodeficiency virus (HIV) prevalence in the district population (P < 0.001) as well as lower HIV co-infection rates (P < 0.001) among new TB cases.CONCLUSION: Relapse and other previously treated TB cases contributed substantially to the notified TB burden in several South African health districts, particularly those with high case notification rates and lower antenatal HIV prevalence. Additional efforts to prevent TB among previously treated people, such as strengthening treatment monitoring and/or secondary preventive therapy, should be considered.