Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis and is spread from person to person through the air. TB can be spread in congregate settings, such as school environments, to varying degrees, based on factors including duration of contact and air ventilation (1); therefore, evaluating potential contacts and exposures can be challenging. In February 2015, a student at a Kansas high school received a diagnosis of active pulmonary TB disease. Screening of 385 (91%) school contacts, four (100%) household contacts, and 19 (90%) social contacts resulted in the identification of 50 persons with latent TB infection. Johnson County Department of Health and Environment (JCDHE) Public Health Emergency Preparedness personnel used their experience with points of distribution logistics to optimize testing clinic layouts and implement the incident command structure. Open communication with students, school staff members, the public, and the media about the investigation from the outset was imperative to reduce rumors and unease that can accompany a large communicable disease investigation. The large number of persons needing treatment for latent TB overwhelmed JCDHE's two TB nurses. As a result, JCDHE developed a policy and procedure to allow persons who met eligibility requirements to complete 12 weekly doses of isoniazid and rifapentine treatment using video directly observed therapy (VDOT) rather than traditional in-person directly observed therapy (DOT). This procedure facilitated treatment compliance and completion; among the eligible 15 persons who chose the 12-week VDOT option, 14 (93%) completed treatment. State and local health departments might consider use of VDOT to monitor treatment of persons with latent TB infection.