To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in lowand middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40-80% efficacy, and to be targeted at "infants" or "adolescents/adults." Vaccine prices were tiered by income group (US $1.50-$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024-2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11-24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42-1.58) million TB cases could be prevented at $1,692 ($634-$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle-, and upper-middleincome countries, respectively. Increased investments in adulttargeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies. mathematical modeling | epidemiology | threshold analysis T he bacterium Mycobacterium tuberculosis was responsible for ∼8.6 million cases of tuberculosis (TB) disease and ∼1.3 million deaths in 2012 (1), of which over 80% were in lowincome countries (LICs) and middle-income countries. This burden remains despite the widespread use of the infant TB vaccine, bacille Calmette-Guérin (bacillus Calmette-Guérin) (2). Dramatic levels of control are required to reach the World Health Organization (WHO) targets of TB elimination as a public health problem by 2050 (3). Previous mathematical modeling has suggested elimination can only be achieved through the use of new vaccines (4-7).In 2013, there were more than a dozen new TB vaccines in clinical trials, using a large range of antigens and adjuvants (8). A variety of modes of action and target populations are being researched (9, 10). The most recent TB vaccine tested in a largescale phase II trial reported a nonsignificant impact on TB disease of 17.3% [95% confidence interval (CI): −31.9 to 48.2] (11). However, such an undertaking highlights the progress that has been made in TB vaccine clinical trials, as well as the need for a reevaluation of the potential impact and need for increased investment in new TB vaccines (12).Estimates of the likely impact and cost-effectiveness of new products before and during development are useful for informing target product profiles and guiding produc...