Only 3% of the nation's 10-15 million residents with latent tuberculosis infection (LTBI) are treated annually, of which approximately half fail to complete the recommended 9-month treatment leaving them at risk for developing tuberculosis (TB) disease. Given that U.S. TB control measures have produced consistent declines in TB disease incidence every year since 1993, LTBI treatment to prevent progression to active TB is vital for TB elimination. The CDC's recent approval of a short-course LTBI treatment regimen consisting of 3 months of weekly isoniazid [H] and rifapentine [P] (3HP)found to be as effective as 9 months of daily self-administered isoniazid (9H-SAT)could profoundly increase treatment initiation and completion rates. However, 3HP must be delivered via directly observed therapy (DOT) to ensure all doses are taken as scheduled. Since DOT is labor intensive, transportation dependent, limited to business hours, inconvenient for patients, and impractical when patients travel or live far from health clinics, adoption by TB control programs is limited. Video DOT (VDOT) is a mHealth application that we developed to allow patients to record and send videos of them ingesting medications, which are watched by TB care providers to document treatment adherence. An NIH- funded pilot study (R21-AI088326; PI: Garfein) among patients treated for TB disease showed >94% adherence with high patient acceptance and significantly reduced costs compared to in-person DOT. The proposed randomized controlled trial will test whether monitoring patients receiving 3HP with VDOT achieves higher treatment completion rates with greater patient acceptability at lower cost than 3HP with clinic-based in-person DOT. The study will: compare treatment completion and adherence rates between patients on VDOT versus in-person DOT and will identify patient factors associated with these outcomes (Aim 1); measure differences in patient acceptability between those monitored with VDOT versus in-person DOT and identify factors associated with acceptance (Aim 2); and, measure cost-effectiveness of VDOT versus in-person DOT for 3HP (Aim 3). Willing patients prescribed 3HP by their physicians, will be randomly assigned (n=155/arm) to be monitored by VDOT or in-person DOT. Participants will mainly include TB contacts, newly arrived refugees and immigrants, and persons with untreated HIV infection because they are at greatest risk for reactivation of LTBI. Effective and affordable methods to monitor treatment adherence for myriad health conditions are greatly needed given that poor adherence can produce drug-resistant pathogens and undermine proven effective treatments for these diseases. Study results will have immediate and direct impacts on public health practice for TB elimination, and provide evidence to support using VDOT to monitor adherence for other health conditions and clinical trials research. This study addresses the urgent need for cost-effective means of combatting the acquisition, development and transmission of TB and drug resistant TB.