In May, 2016, WHO endorsed a 9 month regimen for multidrug-resistant tuberculosis that is cheaper and potentially more effective than the conventional, longer (20–24 month) therapy. We aimed to investigate the population-level implications of scaling up this new regimen. In this population modelling analysis, we developed a dynamic transmission model to simulate the introduction of this short-course regimen as an instantaneous switch in 2016. We projected the corresponding percentage reduction in the incidence of multidrug-resistant tuberculosis by 2024 compared with continued use of longer therapy. In the primary analysis in a representative southeast Asian setting, we assumed that the short-course regimen would double treatment access (through savings in resources or capacity) and achieve long-term efficacy at levels seen in preliminary cohort studies. We then did extensive sensitivity analyses to explore a range of alternative scenarios. Under the optimistic assumptions in the primary analysis, the incidence of multidrug-resistant tuberculosis in 2024 would be 3·3 (95% uncertainty range 2·2–5·6) per 100 000 population with the short-course regimen and 4·3 (2·9–7·6) per 100 000 population with continued use of longer therapy—ie, the short-course regimen could reduce incidence by 23% (10–38). Incidence would be reduced by 14% (4–28) if the new regimen affected only treatment effectiveness and by 11% (3–24) if it affected only treatment availability. Under more pessimistic assumptions, the short-course regimen would have minimal effect and even potential for harm—eg, when 30% of patients are ineligible for the new regimen because of second-line drug resistance, we projected a change in incidence of −2% (−20 to +28). The new regimen's effect was greater in settings with more ongoing transmission of multidrug-resistant tuberculosis, but results were otherwise similar across settings with different levels of tuberculosis incidence and prevalence of multidrug resistance. The short-course regimen has potential to substantially lessen the multidrug-resistant tuberculosis epidemic, but this effect depends on its long-term efficacy, its ability to expand treatment access, and the role of second-line drug resistance. US National Institutes of Health and Bill & Melinda Gates Foundation.