Author summary Why was this study done? Drug resistance poses a major barrier to the effective treatment of tuberculosis, especially in Moldova and other post-Soviet states which have the highest levels of resistance in the world. Individuals with tuberculosis resistant to the key drug rifampicin face a worse prognosis, a longer and more expensive course of treatment, and more side effects than individuals with rifampicin-susceptible tuberculosis. Until recently, the standard of care for rifampicin-resistant tuberculosis (RR-TB) involved many drugs in combination, often given for 18 months or longer. The newer, 6-month “BPaLM” regimen is comprised of 4 drugs (bedaquiline, pretomanid, linezolid, and moxifloxacin) to which resistance levels are currently low, and while it was shown to be just as effective as the standard of care when health outcomes were measured at 72 weeks from treatment initiation, its effect on lifetime health outcomes, costs, and the acquisition of drug resistance was less clear. What did the researchers do and find? Using a mathematical model, we projected the lifetime health benefits and costs of the 6-month BPaLM regimen as compared to 9–18 month, standard of care treatments for RR-TB, and found that 6 months of BPaLM would be likely to provide similar health benefits, at lower cost. Compared to the standard of care, we also found that the 6-month BPaLM regimen could shorten the average duration of tuberculosis resistant to the drugs amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it may increase the average duration of tuberculosis resistant to delamanid and pretomanid. For individuals receiving BPaLM who had to stop taking the drug moxifloxacin, we found that it would likely be beneficial on both health and cost grounds to replace it with clofazimine, thereby topping the regimen back up to 4 drugs. What do these findings mean? Using conventional benchmarks for value-for-money, we estimated that 6 months of BPaLM would be a cost-effective approach for the treatment of RR-TB in Moldova, and potentially other post-Soviet countries. Though the impact of the 6-month BPaLM regimen on the spread of drug resistance is uncertain and not addressed directly by this study, this combination of newer drugs appears to achieve cure more quickly, thereby reducing the amount of time an individual is potentially infectious. This may be beneficial in fighting resistance to several drugs, even while it may increase the spread of resistance to others. Further studies may be warranted to explore how well these findings would translate to different global regions where health system capabilities, costs, and existing resistance patterns may differ.