We conducted a retrospective study of 2555 DR-TB patients admitted to treatment between 2010 and 2016 in six geopolitical zones in Nigeria. We characterized the gender distribution of DR-TB cases and the association between demographics and clinical data, such as age, treatment category, number of previous TB treatment cycles, and geopolitical zone, with gender. The independent effects of being a male or female DR-TB patient were determined using bivariate and multivariate analyzes with statistical significance of < 0.05 and a 95% confidence interval. Records from a total of 2555 DR-TB patients were examined for the study. A majority were male (66.9%), largest age-group was 30-39 years old (35.8%), most had MDR-TB (61.4%), were HIV-negative (76.6%), and previously treated for TB (77.1%). The southwest treatment zone had the highest proportion of DR-TB patients (36.9%), and most DR-TB diagnoses occurred in 2016 (36.9%). On bivariate analysis, age, HIV status, treatment zone, and clinical patient group in DR-TB were significantly associated with male gender. On multivariate analysis, males aged 20-29 years (AOR: 0.19, 95% CI: 0.33-0.59, = 0.001) and HIV-positive males (AOR: 0.44, 95% CI: 0.33-0.59, = 0.001) had lower likelihood of MDR-TB as males in the south-south treatment zone (AOR: 1.88, 95% CI: 1.23-2.85, = 0.03), and being male and aged ≥60 years (AOR: 2.19, 95% CI: 1.05-4.54, = 0.036) increased the probability of DR-TB. The older male population from south-southern Nigeria and women of childbearing age had lower incidence of DR-TB than men of the same age. Tailored interventions to reduce HIV and DR-TB prevalence in the general population, particularly among women of childbearing potential, and treatment support for young and older men are relevant strategies to reduce DR-TB in Nigeria.