The most common cause of treatment failure in tuberculosis is poor patient compliance. TB therapy requires prolonged multi-drug regimens, often lasting 6 months or more, and missing doses can lead to incomplete bacterial eradication. This fosters the development of drug resistance and clinical relapse. Ensuring adherence is critical to achieving cure, preventing transmission, and avoiding multidrug-resistant TB. Other factors like drug toxicity or incorrect diagnosis are less frequently the primary cause of treatment failure. Thus, patient education and support to improve compliance remain cornerstone strategies in TB management.

Reference: Harrison's Principles of Internal Medicine, Braunwald et al., 20th Edition.