Setting: Tuberculosis (TB) patients in Mekelle Zone, Tigray Region, in Ethiopia. Objective: To investigate adherence to anti-tuberculosis treatment. Design: A cross-sectional study in health facilities providing anti-tuberculosis treatment was conducted. Adherence was measured in three ways: through self-reported missed doses, by visual analogue scale whereby patients rate their own adherence and by record review. A patient was considered to be adherent if 90% or more of the prescribed medication was taken. Result: Of 278 TB patients included, 101 were in the intensive and 177 in the continuation phase. Respectively 67 (24.1%), 130 (46.8%) and 80 (28.8%) patients had smear-positive, smear-negative and extra-pulmonary TB. Self-report of missed doses and record review indicated adherence of respectively 273 (97.3%) and 271 (97.5%) patients. By visual analogue scale, 250 (91.6%) patients rated themselves as adherent. History of drug side effects (aOR 0.25, 95%CI 0.08–0.77) and knowledge about TB prevention (aOR 0.19, 95%CI 0.05–0.8) were independently associated with being adherent in this setting. Conclusion: Adherence to anti-tuberculosis treatment was high in our study. Adherence support should be given to the poor, the elderly, patients co-infected with the human immunodeficiency virus, alcohol abusers and smokers. Health education on TB prevention should be given to all TB patients regularly.