The factors related to the outcome of 51 cases of multi-drug-resistant tuberculosis (MDR-TB) reported in 1994 to the French National Reference Center were retrospectively analyzed. The patients (median age, 45 yr) were mainly male (75%), foreign-born (63%), and had pulmonary involvement (95%). Sixteen percent were human immunodeficiency virus (HIV)-coinfected. The number of drugs to which the Mycobacterium tuberculosis isolates were susceptible was four. Only 82% of the patients have been hospitalized at any time (median duration, 33 d). Five patients (9%) received no antituberculosis drugs, although three had drug susceptibility results, indicating that two or more active drugs were available; 46 (91%) received drugs, including 37 who received two or more active drugs. Among the nine cases who received only one active drug, three had drug susceptibility results, indicating that two or more active drugs were available. By December 1996, 10 patients were lost before treatment completion, 24 had treatment failure, and 17 had a favorable outcome. The median survival time was 31 mo. Factors related to a poorer outcome were HIV-coinfection (hazard ratio [HR] = 41), treatment with less than two active drugs (HR = 9.9), and MDR status knowledge at the time of diagnosis (HR = 3.3). The country of birth was not associated with a poorer outcome. The management and outcome of MDR-TB in France has to be improved. A solution would be to develop a specialized unit or team for the treatment of MDR-TB, as recommended by the World Health Organization (WHO).