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Background: In-person directly observed therapy (DOT) is standard of care for tuberculosis (TB) treatment adherence monitoring in the US, with increasing use of video-DOT (vDOT). In Minneapolis, vDOT became available in 2019. Objective: In this paper, we aimed to evaluate the use and effectiveness of vDOT in a program setting, including comparison of verified adherence among those receiving vDOT and in-person DOT. We also sought to understand the impact of COVID-19 on TB treatment adherence and technology adoption. Methods: We abstracted routinely collected data on individuals receiving therapy for TB in Minneapolis, MN, between September 2019 and June 2021. Our primary outcomes were to assess vDOT use and treatment adherence, defined as the proportion of prescribed doses (7 days per week) verified by observation (in person versus video-DOT), and to compare individuals receiving therapy in the pre-COVID-19 (before March 2020), and post-COVID-19 (after March 2020) periods; within the post-COVID-19 period, we evaluated early COVID-19 (March-August 2020), and intra-COVID-19 (after August 2020) periods. Results: Among 49 patients with TB (mean age 41, SD 19; n=27, 55% female and n=47, 96% non-US born), 18 (36.7%) received treatment during the post-COVID-19 period. Overall, verified adherence (proportion of observed doses) was significantly higher when using vDOT (mean 81%, SD 17.4) compared to in-person DOT (mean 54.5%, SD 10.9; P=.001). The adoption of vDOT increased significantly from 35% (11/31) of patients with TB in the pre-COVID-19 period to 67% (12/18) in the post-COVID-19 period (P=.04). Consequently, overall verified (ie, observed) adherence among all patients with TB in the clinic improved across the study periods (56%, 67%, and 79%, P=.001 for the pre-, early, and intra-COVID-19 periods, respectively). Conclusions: vDOT use increased after the COVID-19 period, was more effective than in-person DOT at verifying ingestion of prescribed treatment, and led to overall increased verified adherence in the clinic despite the onset of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]