Tuberculosis (TB) is a global health concern. Treatment is prolonged, and patients on anti-TB therapy (ATT) often experience treatment failure for various reasons. There is an urgent need to identify signatures for early detection of failure and initiation of a treatment switch.We investigated how gene biomarkers and/or basic patient characteristics could be used to define signatures for treatment outcomes in Indian adult pulmonary-TB patients treated with standard ATT. Using blood samples at baseline, a 12-gene signature combined with information on gender, previously-diagnosed TB, severe thinness, smoking and alcohol consumption was highly predictive of treatment failure at 6 months. Likewise a 4-protein biomarker signature combined with the same patient characteristics was almost as highly predictive of treatment failure. Combining biomarkers and basic patient characteristics may be useful for predicting and hence identification of treatment failure at an early stage of TB therapy.