The effectiveness of Video Observed Therapy (VOT) for treating Tuberculosis (TB) has not been measured in low and middle-income countries (LMICs), where more than 95% of TB cases and deaths occur. In this study, we analyse the effectiveness, and patient cost-difference, of VOT compared to clinic-based Directly Observed Therapy (DOT) in improving medication adherence in Moldova, a LMIC in Eastern Europe.The study was a 2-arm individually randomised trial with 197 TB patients (n=99 in DOT control group; 98 in VOT treatment group, MDR-TB cases were excluded). The primary outcome was observed medication adherence, measured by the number of days that a patient failed to be observed adhering to medication for every two-week period during the course of their treatment RESULTS: VOT significantly decreased non-adherence by 4 days (95% CI, 3.35 to 4.67 days; p<0.01) per two-week period: 5.24 days missed per two-week period for DOT and 1.29 days for VOT. VOT patients spent 504 Moldovan Leu (MDL) (approximately €25; 95% CI, 277 to 730 MDL; p<0.01) and 58 h (95% CI, 48 to 68 h; p<0.01) less on their treatment. VOT also increased self-reported satisfaction with treatment. We found no significant results pertaining to treatment success, patient well-being or patient employment status and some evidence of an increase in side effects.In this trial, Video Observed Therapy (VOT) increased observed medication adherence for tuberculosis patients in Moldova, a LMIC, when compared to clinic-based Directly Observed Therapy (DOT). VOT also significantly reduced the time and money patients spent on their treatment.