Patients who suffered drug reaction with eosinophilia and systemic symptom (DRESS) during the treatment of tuberculosis (TB) commonly experience multidrug hypersensitivity reactions resulting in limited anti-TB drug choices. Therefore, reintroduction based on a desensitization protocol may be an option to resume anti-TB medication. To evaluate the outcomes and safety of resuming anti-TB drugs according to reintroduction methods in patients with anti-TB drug-related DRESS. A retrospective cohort of patients who had experienced anti-TB drug-related severe cutaneous adverse reactions from 2011 to 2017 was established from separate 5 institutions. Anti-TB medication was resumed in 27 of 29 patients with anti-TB drug-related DRESS through complete changing regimen (n= 9), reintroduction by a graded challenge (n= 5), or reintroduction using a desensitization protocol (n= 13). Nine patients completely changed their anti-TB regimen to second-line TB drugs, but only 1 (11.1%) succeeded in maintaining new anti-TB drugs. The other 8 failed to take drugs due to the occurrence of hypersensitivity reactions to the newly introduced anti-TB drugs. Two (40.0%) of 5 patients who underwent graded rechallenges successfully completed anti-TB drugs, whereas 3 (60%) failed to resume anti-TB drugs due to the recurrence of hypersensitivity reactions. In 13 patients who resumed anti-TB drugs using a desensitization protocol, no one who underwent desensitization developed recurrence of DRESS; 11 (84.6%) eventually completed anti-TB treatment and 2 eventually failed to complete anti-TB treatment due to late-onset itching and drug-induced liver injury. Resuming anti-TB medication based on desensitization protocols may be a safe and effective option for those with anti-TB drug-related DRESS.