SETTING AND OBJECTIVE: To describe trends in drug-resistant tuberculosis (TB) in two gold-mining workforces, South Africa, 2002-2008. DESIGN: TB programme data analysis. RESULTS: TB case notification rates decreased between 2002 and 2008 from 4006 to 3018 per 100,000 and from 3192 to 2468/100,000 for Companies A and B, respectively. Human immunodeficiency virus (HIV) prevalence exceeded 80% in TB episodes with known status. The proportion of TB episodes with multidrug-resistant TB (MDR-TB) increased from 6/129 (4.7%) to 17/85 (20.0%) among previously treated cases, and from 4/38 (10.4%) to 7/28 (25.0%) in Companies A and B, respectively (tests for trend, Company A, P < 0.001; Company B, P = 0.304). Case notifications of MDR-TB increased during 2002-2008 from 39.8 to 122.9/100,000/year in Company A and from 7.8 to 96.8/100,000/year in Company B. Coverage of second-line drug susceptibility testing (DST) among MDR-TB episodes was low. Previous treatment exposure was a strong risk factor for MDR-TB (prevalence ratio 8.78, 95%CI 5.94-12.97 in previously treated vs. untreated individuals). CONCLUSION: Despite decreasing TB notifications overall, MDR-TB notifications and proportions of episodes with MDR-TB increased in the larger company. Cure must be ensured in first episodes to prevent acquired resistance. Improved coverage of culture, DST and HIV testing is required to allow treatment to be optimised.