Achieving ambitious targets to address the global tuberculosis (TB) epidemic requires consideration of the impact of competing interventions for improved identification of patients with TB. Cost-effectiveness analysis (CEA) and benefit-cost analysis (BCA) are two approaches to economic evaluation that assess the costs and effects of competing alternatives. However, the differing theoretical basis and methodological approach to CEA and BCA is likely to result in alternative analytical outputs and potentially different policy interpretations. A BCA was conducted by converting an existing CEA on various combinations of TB control interventions in South Africa using a benefits transfer approach to estimate the value of statistical life (VSL) and value of statistical life year (VSLY). All combinations of interventions reduced untreated active disease compared to current TB control, reducing deaths by between 5,000 and 75,000 and resulting in net benefits of Int$3.2–Int$137 billion (ZAR18.1 billion to ZAR764 billion) over a 20-year period. This analysis contributes to development and application of BCA methods for health interventions and demonstrates that further investment in TB control in South Africa is expected to yield significant benefits. Further work is required to guide the appropriate analytical approach, interpretation and policy recommendations in the South African policy perspective and context.