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We assessed video directly observed therapy (VDOT) for monitoring tuberculosis treatment in 5 health districts in California, USA, to compare adherence between 174 patients using VDOT and 159 patients using in-person directly observed therapy (DOT). Multivariable linear regression analyses identified participant-reported sociodemographics, risk behaviors, and treatment experience associated with adherence. Median participant age was 44 (range 18–87) years; 61% of participants were male. Median fraction of expected doses observed (FEDO) among VDOT participants was higher (93.0%[interquartile range (IQR) 83.4%–97.1%]) than among patients receiving DOT (66.4%[IQR 55.1%–89.3%]). Most participants (96%) would recommend VDOT to others; 90% preferred VDOT over DOT. Lower FEDO was independently associated with US or Mexico birth, shorter VDOT duration, finding VDOT difficult …