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Background: Despite the high efficacy of tuberculosis (TB) drug regiments, one of the barriers in the TB control program is the non-compliance to treatment. Morbidity, mortality, and risk to become resistant to drugs are emerging among defaulters. Thus, the aim of this study is to identify the factors, especially knowledge and perceptions of TB and association with treatment default among patients treated in primary care settings, East Nusa Tenggara. Methods: This study was part of a bigger cohort community-based controlled trial study. The subjects were newly diagnosed pulmonary TB patients from four districts in East Nusa Tenggara. Knowledge, perception of TB, and other related factors were assessed prior to the treatment. Patients who interrupted the treatment in two consecutive months were classified as defaulters, as World Health Organization stated. Odds ratio (OR) looking for factors associated with becoming defaulter was analyzed. Results: A total of 300 patients were recruited for this study. At the end of the treatment, 255 patients (85%) completed the treatment without interruption from regular visit. In univariate analysis, none of the socio-demographic factors attributed to treatment default yet lack of knowledge and incorrect perception of TB prior therapy (OR 2.49 1.30-4.79 95% Cl, p = 0.006; OR 5.40 2.64-11.04 95% Cl, p < 0.001, respectively). In multivariate analysis, only incorrect perception of TB showed significant association with treatment default (OR 4.75 2.30-9.86 95% Cl). Conclusions: Assessing the knowledge and perception of TB prior to the treatment in newly pulmonary TB patients is important as both of them were known as risk factor for treatment default. Education and counseling may be required to improve patients' compliance to treatment. [ABSTRACT FROM AUTHOR]