BACKGROUND: Rifampicin mono-resistant tuberculosis (RMR-TB) is a rare disease and current guidelines recommend that RMR-TB should be treated as multidrug-resistant TB (MDR-TB) but the evidence is scarce. Methods: We conducted a retrospective study to investigate the characteristics and outcomes of RMR-TB. The characteristics of RMR-TB were compared with those with adverse events to rifampicin (RAE-TB). Results: From 1999 to 2013, 44 RMR-TB and 29 RAE-TB patients were enrolled. The RMR-TB had more alcohol use, prior history of TB and radiologically severe diseases compared with the RAE-TB. The RAE-TB had more comorbidities and combined extrapulmonary TB than RMR-TB. The median treatment duration was 450 days in RMR-TB and 324 days in RAE-TB (p=0.001) and time to culture conversion was 93 days and 64 days, respectively (p=0.020). Treatment success rates were 87.2% (34/39) and 80.0% (20/25), respectively (p=0.586). When the RMR-TB was divided into 3 groups according to the treatment regimens (Group 1 = 1st-line regimen, n=11; Group 2= 1st-line + quinolone regimen, n=12; Group 3= MDR-TB regimen, n=21), Group 3 was radiologically more severe but other characteristics were similar between groups. Even though the treatment duration was different between groups, 345 days, 405 days and 528 days, respectively, treatment success rates were not different between groups, 85.7% (6/7), 91.7% (11/12) and 85.0% (17/20), respectively. Conclusions: The shorter treatment duration may be enough to treat RMR-TB compared with MDR-TB, in some patients even with 1st-line drugs alone.