Background: Nigeria is one of the 30 high burden countries for drug resistant tuberculosis (DR-TB). This study assessed the prevalence and factors associated with rifampicin resistant tuberculosis (RR-TB) in a secondary referral hospital in Lagos State Nigeria. Methods: A retrospective review of presumptive TB register of patients screened for Mycobacterium tuberculosis (MTB) and RR-TB using Xpert MTB/RIF assay at Mainland hospital between January 1 2012 and December 31 2016 was conducted. Results: A total of 2497 clients were screened for MTB and RR-TB during the study period. The majority (51.4%) were between 25 – 44 years. Male: Female ratio was 1:0.8. Of the 2497 clients screened, MTB was detected in 942 (37.7%) out of which 220 (23.4%) had RR-TB. Age (AOR 1.8, 95%CI 1.3- 2.6, p = 0.001), symptomatic contact with DR-TB patients (AOR 3.3, 95%CI 2.1-5.1, p <0.001) and type of TB (AOR 2.9, 95% CI 1.7 – 5.0, <0.001) were associated with RR-TB after adjusting for age, gender, HIV status and symptomatic contacts with DR-TB patients. Conclusion: The prevalence of RR-TB in new and previously treated TB patients was high in this study. Urgent steps are needed to avert an impending RR-TB epidemic