Abstract: Objective To understand the drug-resistance situation among patients with smear-positive pulmonary tuberculosis (PTB) in Foshan city and to provide evidence for policy making of TB control.Methods All smear-positive PTB patients newly registered from February 2008 to February 2013 in the Global Fund multi-drug resistance TB (MDR-TB) project in Foshan City were enrolled in this study. Drug-susceptibility testing (DST) for Mycobacterium tuberculosis complex strains from enrolled patients was performed, and to the 4 first-line anti-TB drugs including Sm, INH, RFP and EMB. SPSS software, version 16.1 was used for statistical analysis. χ² test was used to compare difference in drug-resistance patterns between different groups of patients, and a significance level was P<0.05.Results A total of 1924 smear-positive PTB patients were enrolled in this study, and results of DST were available for 1 375 patients. The total resistance rate of smear-positive PTB patients was 28.80% (396/1375), respectively 20.55% (215/1046) for new smear-positive PTB patients and 55.02% (181/329) for retreatment smear-positive PTB patients. The total MDR-TB rate of smear-positive PTB patients was 11.71% (161/1375), respectively 3.82% (40/1046) for new patients and 36.78% (121/329) for retreatment patients. Mycobacterium tuberculosis strains isolated from the enrolled new patients had the highest rate of any resistance to Sm (15.77%, 165/1046), followed by resistance to INH (9.08%, 95/1046), RFP (5.93%, 62/1046) and EMB (3.35%, 35/1046); Mycobacterium tuberculosis strains isolated from the enrolled retreatment patients had the highest rate of any resistance to INH (45.29%, 149/329), followed by resistance to RFP (40.73%, 134/329), Sm (32.83%, 108/329) and EMB (20.36%, 67/329). The drug-resistance rates of patients in different age groups: 12.50% (2/16) in patients aged 7-17 years, 30.28% (195/644) in patients aged 18-39 years, 28.37% (141/497) in patients aged 40-59 years, 26.61% (58/218) in patients aged 60 years and above; there was no significant difference in the drug-resistant rate among patients of different age groups (χ²=0.03-6.39, P>0.05). The drug-resistance rates of male and female patients were 27.58% (275/997) and 32.01% (121/378) respectively, there was no significant difference in drug-resistance rate between male and female patients (χ²=2.62, P>0.05). The drug-resistance rates of patients from resident and floating population were 29.90% (180/602) and 27.94% (216/773) respectively, there was no statistically significant difference in drug-resistance rate between patients of different population groups (χ²=0.63, P>0.05).Conclusion The drug-resistance of patients with smear-positive PTB is in a serious condition in Foshan City. Studies on methods of TB treatment and management should be strengthened.