A step-wise approach to identify valid and feasible methods to detect non-adherence to tuberculosis drugs was evaluated in a prospective study among pulmonary tuberculosis patients in an outpatient clinic in Indonesia. First, adherence was measured by self-reporting with the standardized Morisky questionnaire, physician assessment, pill-count, visit attendance, diary and an electronic medication event monitoring system (MEMS). Next, validity of single methods was assessed against MEMS as gold standard. Feasibility of methods was then judged by physicians in the field. Finally, when valid and feasible methods were combined, it appeared that self-reporting by a questionnaire plus physician assessment could identify all non-adherent patients. It is recommended to use a systematic approach to develop a valid and locally feasible combination of methods to detect non-adherence to TB drugs.