Study objectives: Previous studies have had difficulty evaluating the optimal clinical site for screening homeless patients for active tuberculosis (TB). We hypothesized that homeless patients with TB would not frequently reside in shelters at the time of their diagnosis and would be more likely than other patients with TB to seek care in public hospitals, thus presenting an opportunity for screening radiography. Methods: This registry-based survey included 743 consecutive patients with confirmed active TB in Los Angeles County. No therapeutic intervention was involved. Results: When compared with patients with TB who were not homeless, homeless patients with TB were more likely to be male (93% versus 63%, P<.001), black (44% versus 15%, P<.001), living in the inner city (55% versus 7%, P<.001), and born in the United States (67% versus 32%, P<.001). They were more infectious than other patients with TB as evidenced by a trend toward more cavitary radiographic lesions (24% versus 16%, P=.11) and significantly more positive sputum smears (56% versus 41%, P=.009). Less than a third lived in congregate facilities such as shelters at the time of their diagnosis. Instead, their disease was diagnosed more often at county hospitals (54% versus 23%, P<.001) than patients with TB who were not homeless. Conclusion: Widespread screening for TB in shelters may miss most homeless patients with TB. Because most county-hospital homeless patients with TB initially present to emergency departments and many do not live in shelters, future cost-effectiveness studies should evaluate chest radiograph screening for all homeless ED patients. (Authors)