BACKGROUND: Despite considerable efforts to globally eradicate TB, and the availability of effective antibiotics, TB elimination goals are falling behind. While non-adherence to TB drug regimens may compromise effective treatment, its full impact is still unknown.OBJECTIVE: To determine the clinical and economic impact of non-adherence to TB medication on treatment outcomes in drug-susceptible TB patients (DS-TB).METHODS: A systematic review was performed using PubMed and Embase for studies published between 2009 and 2019 reporting associations between adherence and WHO-defined TB treatment outcomes and economic outcomes in DS-TB patients.RESULTS: A total of 14 studies were included. Eight focused on the association between non-adherence and death, 2 on treatment failure, 1 study on successful treatment outcome, 1 study on both successful and unsuccessful treatment outcomes and 2 on cost outcomes. Most studies (71.4%) were retrospective cohort or case-control studies. The results showed that non-adherence to TB drug regimens was associated with death, treatment failure and lower cure rates.CONCLUSION: Non-adherence to TB drugs has a profound impact on both clinical and economic TB outcomes. To reach WHO TB elimination goals, preventing non-adherence and the implementation of cost-effective intervention programmes should receive the highest priority.