Abstract: Introduction: Drug-resistant TB poses a significant threat to global TB care and prevention and remains a major public health issue in many countries and Testicular drug-resistant tuberculosis (testicular DR-TB) refers to a form of tuberculosis that specifically affects the testicles and is resistant to standard anti-TB medications, isolated testicular involvement is uncommon. Case presentation: a twenty-seven-year-old male patient presented with painful swelling of the scrotum for one month. He was treated with first-line anti-TB (RHZE/RH) and completed a month back at the health center. He had a similar complaint during the first diagnosis. While he was on treatment, the swelling subsided and recurred while he discontinued the medication. Our hospital received a referral for this complaint. Otherwise, he has no history of chronic illness, no surgical procedure at any site, no usage of second-line anti-TB drugs, or contact with a DR-TB patient. During the presentation, his vital signs were within normal range. The only pertinent finding was in the genitourinary system, which is that the scrotum is swollen and tender. Following clinical examinations and investigation findings with the diagnosis of RR-EPTB (testicular TB), we put him on an individualized longer regimen (Lfx/Cs/Cfz/Bdq/Cfz/Lzd) and pyridoxine. After 18 months of treatment, the outcome is declared as completed. After being advised on danger signs, he was appointed after six months for post-treatment follow-up according to the Ethiopian DR-TB management protocol. Conclusion: This case highlights the importance of timely diagnosis and adherence to treatment in managing drug-resistant extrapulmonary tuberculosis (RR-EPTB), specifically testicular TB. The patient's recurrent symptoms following discontinuation of first-line anti-TB therapy illustrate the challenges faced in treatment adherence and the potential consequences of inadequate management.Abstract: Introduction: Drug-resistant TB poses a significant threat to global TB care and prevention and remains a major public health issue in many countries and Testicular drug-resistant tuberculosis (testicular DR-TB) refers to a form of tuberculosis that specifically affects the testicles and is resistant to standard anti-TB medications, isolated testic...Show More