Since the early 1990s, an increase in Mycobacterium tuberculosis drug resistance has been reported, with high prevalence among HIV+ patients. We evaluated the sensitivity patterns of M. tuberculosis, resistance rate, and predisposing factors among HIV+ patients in Santos, São Vicente, Cubatão, Praia Grande, and Guarujá, São Paulo State, Brazil. The medical charts of 301 patients with positive cultures for M. tuberculosis from 1993 to 2003 were reviewed. Resistance occurred in 57 patients (18.9%), as follows: 32 (10.6%) displayed multidrug-resistant tuberculosis (resistant to at least Rifampicin and Isoniazid); 4 (1.3%) were resistant to two or more drugs; and 21 (7%) were resistant to a single drug. Acquired resistance was observed in 70.1% of cases. Drug resistance was significantly associated with previous tuberculosis treatment, duration of HIV diagnosis, and previous hospitalization. In logistic regression analysis, only previous tuberculosis treatment adjusted by age remained as an independent risk factor (OR = 5.49; 95%CI: 2.60-11.60). Drug resistance to at least one drug in 18.9% and multidrug resistance in 10.6% of cases highlight the relevance of this problem in HIV patients in the Baixada Santista.