BACKGROUND: The burden of non-adherence to anti-tuberculosis (TB) treatment is poorly understood. One type is early discontinuation, that is, stopping treatment early. Given the implications of early discontinuation for treatment outcomes, we undertook a systematic review to estimate its burden, using the timing of loss to follow-up (LFU) as a proxy measure. METHODS: Web of Science, Embase and Medline were searched up to 14 January 2021 using terms covering LFU, TB and treatment. Studies of adults (≥ 18 years) on the standard regimen for drug-sensitive TB reporting the timing of LFU (WHO definition) were included. A narrative synthesis was conducted and quality assessment undertaken using an adapted version of Downs and Black. Papers were grouped by the percentage of those who were ultimately LFU who were LFU by 2 months. Three groups were created: <28.3% LFU by 2 months, ≥28.3-<38.3%, ≥38.3%). The percentage of dose-months missed due to early discontinuation among (1) those LFU, and (2) all patients was calculated. RESULTS: We found 40 relevant studies from 21 countries. The timing of LFU was variable within and between countries. 36/40 papers (90.0%) reported the percentage of patients LFU by the end of 2 months. 31/36 studies (86.1%) reported a higher than or as expected percentage of patients becoming LFU by 2 months. The percentage of dose-months missed by patients who became LFU ranged between 37% and 77% (equivalent to 2.2-4.6 months). Among all patients, the percentage of dose-months missed ranged between 1% and 22% (equivalent to 0.1-1.3 months). CONCLUSIONS: A larger than expected percentage of patients became LFU within the first 2 months of treatment. These patients missed high percentages of dose months of treatment due to early discontinuation. Interventions to promote adherence and retain patients in care must not neglect the early months of treatment. PROSPERO REGISTRATION NUMBER: CRD42021218636.