Background: Tuberculosis (TB) is a leading infectious cause of death globally. Current treatment for drug-susceptible (DS-TB) and rifampicin-resistant (RR-TB) infections is lengthy and toxic. Methods: The STAND trial was a partially-randomised, open-label, non-inferiority phase 3 study. Patients ≥18 years with smear positive sputum were eligible. HIV-positive patients with CD4+ counts <100 cells/mm3 were excluded. DS-TB participants were randomised 1:1:1:1 to receive: 200mg pretomanid (P) daily, 400mg moxifloxacin (M) and 1500mg pyrazinamide (Z) for either 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE) in combination for 6 months as control. The primary outcome was treatment failure or relapse 12 months after randomisation. The non-inferiority margin for between-group differences was 12 percent. RR-TB participants were allocated to 6Pa200MZ. Recruitment was paused in September 2015 and did not resume. Findings: In total 43 of 56 (76.8%), 46 of 61 (75.4%), 38 of 57 (66.7%), and 52 of 60 (86.7%) DS-TB participants were favourable on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ, and control respectively. The difference in favourable response between control and 6Pa200MZ was 9.9% [95%CI -4.1 to 23.9%]. Ten of 11 (90.9%) RR-TB participants were favourable. Grade 3 or higher adverse events affected 22 of 67 (32.8%) 6Pa200MZ participants, 21 of 71 (29.6%) on 4Pa200MZ, 25 of 65 (38.5%) on 4Pa100MZ, and 19 of 68 (27.9%) on control. Serious adverse events affected 19 of 203 (9.4%) experimental DS-TB participants, 3 of 68 (4.4%) on control, and 3 of 13 (23.1%) RR-TB cases. Ten of 203 (5%) participants on the experimental arms and 2 of 68 (3%) participants on the control arm died, with 2 deaths on the 4MPa200Z arm and one death on the 4MPa100Z arm attributed to hepatotoxicity. Interpretation: The experimental DS-TB treatment did not achieve non-inferiority in this underpowered trial. The role of Pa200MZ in tuberculosis treatment needs to be investigated further. Trial Registration: (Clinicaltrials.gov identifier NCT02342886) Funding Statement: Sponsored by TB Alliance with financial support from the U.K. Department for International Development, Bill and Melinda Gates Foundation, U.S. Agency for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and the Federal Ministry for Education and Research of Germany. Declaration of Interests: The authors declared no conflicts of interest. Ethics Approval Statement: Ethical approval was granted by the national and local ethics committees for the sites participating in the trial.