BACKGROUND: Current guidelines for the treatment of multidrug-resistant/rifampin-resistant tuberculosis (MDR/RR-TB) are based on clinical trials evaluating fixed duration regimens. However, when a regimen succeeds, it remains unknown whether a shorter duration could yield the same results. Similarly, if a regimen fails, it is unclear whether extending the treatment could improve outcomes. Trials are needed to assess the relationship between various treatment durations and outcomes. METHODS/DESIGN: We designed a duration-randomized trial of treatment for fluoroquinolone-susceptible MDR/RR-TB. The DRAMATIC (Duration Randomized Anti-MDR-TB And Tailored Intervention Clinical) Trial is a multicenter, randomized, partially blinded, four-arm, phase 2 trial that examines an all oral, pyrazinamide-free regimen of bedaquiline, clofazimine, delamanid, linezolid, and levofloxacin, with administration of linezolid only in the initial 16 weeks of treatment. The four trial arms are treatment durations of 16, 24, 32 and 40 weeks. Randomization is stratified by "extensive" or "non-extensive" disease based on baseline smear (or Xpert) and cavitary status. The primary endpoint is relapse-free survival at week 76. The target sample size is 220. Participants are being enrolled in sites in the Philippines and Vietnam. The expected output will be an equation describing the relationship between treatment duration and the proportion of participants with relapse-free survival. DISCUSSION: This trial aims to demonstrate that a duration-response relationship can be described for the treatment of MDR/RR-TB by a duration-randomized trial.