Background: Information on prevalence of tuberculosis (TB) in Ethiopian prisons is non-existent, despite its highly endemic nature. So, the aim of this study was to determine prevalence and associated risk factors for pulmonary TB (PTB) in three large prisons of Eastern Ethiopia. Methodology: A cross-sectional study was performed on 382 sampled prisoners (44 PTB cases and 338 PTB suspects) from July to November, 2008. A structured questionnaire was administered to prisoners who had ≥ 2 weeks of cough. Sputum samples were analyzed by direct smear microscopy and culture on Löwenstein-Jensen medium. Data were analyzed using logistic regression model. The analysis was evaluated using goodness-of-fit tests.Result: Using an active screening strategy, 371 PTB suspects were identified; out of which, 33(8.9%) were smear- or culture-positive PTB. Eleven (25%) newly diagnosed PTB cases were sharing a cell with already known TB cases. Including 11 PTB cases on anti-TB treatment (passively identified), the point prevalence of PTB was 1913/100,000 (95%CI=1410-2580); about seven times higher than it’s prevalence in the general population. Three previously undetected PTB cases were found for every 1 case that was identified passively. Risk factors for PTB included being an urban resident (AOR=2.79, 95%CI=1.26-6.17), having > 3 visits to clinics for TB symptoms (AOR=3.33, 95%CI=1.15-9.60), cough > 4 weeks (AOR=2.69, 95%CI=1.20-5.98), sharing a cell with a TB patient (AOR=2.82, 95%CI=1.33-6.00) or a prisoner with chronic cough (AOR=3.61, 95%CI=1.68-7.76). Also, high proportion (40.4%) of prisoners had low level of biomedical knowledge of TB. Independent predictors for low knowledge of TB included being an illiterate (AOR=2.22, 95%CI 1.29-3.82), not able to visit health institution for TB symptoms (AOR=2.52, 95%CI 1.41-4.49), had longer duration of cough (> 4 weeks) (AOR=1.77, 95%CI 0.99-3.12), and imprisoned in C (AOR=15.62, 95%CI 7.47-33.54) and B (AOR=2.67 and 95%CI 1.38-5.16) prisons.Conclusion: The present study indicates high prevalence of PTB and associated risk factors that favor the transmission of the causative agent and the acquisition of new cases, and hence dangerous for the prison population and surrounding community. Therefore, active surveillance of TB and implementing specific prevention and control guidelines are highly recommended.