A study was conducted to know the rate of non-compliance of antituberculosis therapy among HIV-infected patients, the factors associated with non-compliance and the evolution of these patients. The therapy compliance in 276 tuberculous HIV infected patients diagnosed in two Madrid hospitals was analyzed. Fifty-one patients (18%) were not included in the analysis (6 died without therapy, 6 were lost and 39 died during therapy). Out of the 225 evaluable patients, 36 (16%, 95% CI, 11.6-21.6) did not comply with therapy. The only factor associated with a higher therapy non-compliance was the antecedent of drug use (20% of non-compliance; relative risk: 10, 95% CI, 1.4-71). Patients using drugs at tuberculosis diagnosis had higher risk for non-compliance (31%; RR, 3.1; 95% CI, 1.6-6.3). The incidence of tuberculosis reactivation after leaving therapy was 78.8/100 patient-years. Therapy non-compliance increased death risk associated with tuberculosis (RR, 9.8; 95% CI, 4.6-21). Programs for controlling antituberculous therapy should give priority to active drug users, as this is the group with the highest risk for non-compliance.