To aid in prioritizing the development of tuberculosis (TB) vaccines most likely to reach the 2050 TB elimination goal, we estimated the impact and cost-effectiveness of a range of vaccine profiles in low- and middle-income countries. Using mathematical modeling, we show that vaccines targeted at adolescents/adults could have a much greater impact on the TB burden over a 2024–2050 time horizon than those vaccines targeted at infants. Such vaccines could also be cost-effective, even with relatively high vaccine prices. Our results suggest that to achieve the 2050 elimination goals, future TB vaccine development should focus on vaccines targeted at adolescents/adults, even if only relatively low efficacies and short durations of protection are technically feasible.