We determined the prevalence of rifampicin resistance in pulmonary tuberculosis patients in Enugu Nigeria. A prospective hospital-based study involving 1300 presumptive multidrug-resistant tuberculosis patients was conducted in Enugu between April 2017 and 31st March, 2019.Participants age ranged from 15 years and older and each submitted one sputum specimens Sputum specimens were analyzed using the Gene Xpert MTB/RIF assay to detect resistance to rifampicin according to manufacturer's protocol. The prevalence of rifampicin resistant tuberculosis was 6.8% (95% CI: 5.5- 8.3). Rifampicin resistance was significantly higher in males (9.0%) than females (4.2%) (P = 0.036< 0.05). Most of the cases were seen in the age group 35-44 years (28.4%). Prevalence of rifampicin resistant tuberculosis was 2.7% in treatment naive (new) patients and 4.1% in patients on anti-tuberculosis therapy (previously treated). The prevalence of rifampicin resistant tuberculosis in Enugu was high. Rifampicin resistance in treatment naive (new) patients was also high. This study therefore highlights that active transmission of Multidrug-resistant tuberculosis among young males could be on-going.