ABSTRACT: BACKGROUND:Tuberculosis (TB) remains a major health problem worldwide and in Ethiopia. This study aimed to investigate the spatial distributions of notified TB over the whole territory of Ethiopia and to quantify the role of health care access, environmental, socio-demographic, and behavioural factors associated with the clustering of TB. METHODS:A spatial analysis was conducted using national TB data reported between June 2016 and June 2017 in Ethiopia. Spatial clustering of TB was explored using Moran's I statistic and the local indicator of spatial autocorrelation (LISA). A multivariate Poisson regression model was developed with a conditional autoregressive (CAR) prior structure and with posterior parameters estimated using Bayesian Markov chain Monte Carlo (MCMC) simulation with Gibbs sampling to investigate the drivers of the clustering. RESULT:A total of 120,149 TB cases were reported from 745 districts in Ethiopia during the study period; 41,343 (34%) were bacteriologically confirmed new pulmonary TB and 33,997 (28%) were clinically diagnosed, new, smear-negative pulmonary TB patients. The nationwide annual incidence rate of notified TB was 112 per 100,000 population. The highest incidence was observed in three city administrative regions, namely Dire Dewa (348 cases per 100,000 population), Addis Ababa (262 per 100,000 population) and Harari (206 per 100,000 population), and the lowest incidence was observed in Somali region (51 per 100,000 population). High-high spatial clustering of notified TB was detected at Humera, Gog, and Surima district, and low-low clustering was detected in some districts located in the Somali region. Poor health care access (IRR = 0.78; 95%CI: 0.66, 0.90) and good knowledge about TB (IRR = 0.84; 95%CI: 0.73, 0.96) were negatively associated with the incidence of notified TB. CONCLUSION:Substantial spatial clustering of notified TB was detected at region, zone and district level in Ethiopia. Health care access and knowledge about TB was associated with incidence of TB. This study may provide policy makers target hotspot areas, where national control programs could be implemented more efficiently for the prevention and control of TB, and to address potential under-reporting in poor access areas.