Interruption in tuberculosis (TB) treatment still remains the most important challenge for control of the disease. This study aimed to identify the determinants of TB treatment default in Fez, Morocco. A 12 pair-matched case–control study was carried out in the TB control units in Fez. Cases were defaulters to TB treatment and were matched by age and sex to non-defaulters (controls). Of the 320 patients (108 defaulters, 212 controls), 80.6% were male. The main reason for defaulting reported by patients was the sensation of being cured. Predictive factors for treatment default in the multivariate conditional logistic regression analysis, were relapsed case (adjusted OR = 4.49; 95% CI 1.87–10.8), current smoking (aOR = 2.10; 95% CI 1.07–4.14), alcohol use (aOR = 2.92; 95% CI 1.04–8.19), being more than 30 minutes away from the health centre (aOR = 3.34; 95% CI 1.06–10.5) and perception of having received insufficient explanation about the disease (aOR = 2.87; 95% CI 1.53–5.36). The rate of defaulting in Fez can be lowered through targeted and realistic measures.