Despite the widespread availability of an efficacious and affordable regimen and strategy for managing drug-susceptible tuberculosis (TB), the emergence of multidrug resistant (MDR) TB remains a major challenge for global TB control efforts. In 2010, data from Bangladesh indicated that a nine-month regimen achieves outcomes comparable to those of the existing, 18-24 month, WHO-approved MDR-TB regimen. The primary objective of the STREAM trial is to assess whether the Bangladesh regimen is non-inferior to the control (WHO approved MDR-TB) regimen. Its practical, programme-based study design will also ensure that if the results are favourable they will be generalisable to routine programme settings. In addition, health system and patient costs associated with implementation will be documented. These will be analysed in association with the clinical outcomes of the trial to provide information for subsequent policy and practice decision-making. The main aim of the health economics component of the STREAM trial is to determine whether a standardised regimen that has been used in one country setting with excellent treatment outcomes is more cost-effective from a health system and patient perspective than the current regimen in those countries.