Abstract Background Rifampicin resistance is a risk factor for poor outcome in tuberculosis. Therefore, we sought to describe the characteristics and management of Rifampicin monoresistant (RMR) tuberculosis (TB) in France. Methods We conducted a retrospective cohort analysis in 2012 on RMR TB patients diagnosed in France between 2005 and 2010 by using a national laboratory network. A standardized questionnaire was used to collect basic demographic data, region of birth, history of TB, HIV-coinfection, alcohol use, and antituberculosis treatment. Outcome was assessed after at least 18 months of follow-up. Results A total of 39 patients with RMR TB were reported (0.12% of all TB cases). Overall, 19 (49%) had a previous history of treatment, 9 (23%) were HIV-coinfected, and 24 (62%) were smear-positive. Patient with secondary RMR were more likely to have alcohol abuse (P = 0.04) and HIV-coinfection (p = 0.04). Treatment outcome could be assessed for 30 patients, the nine others being dead or lost to follow-up. A total of 20 (67%) of the 30 assessed were cured, 3 (10%) died, 3 (10%) relapsed, and 4 (13%) were lost to follow up. Four (13%) received less than 6 months of treatment, 3 did not have any modification of the standardized regimen, 13 (43%) received fluoroquinolones, 4 (13%) aminoglycosides, and 8 (26%) a combination of both. Conclusions RMR TB is a rare disease in France, and its management was heterogeneous. The lack of treatment standardization may be a consequence of low expertise and may lead to the unsatisfactory low success rate.