OBJECTIVE: To investigate the factors associated with the increasing incidence of tuberculosis in England. DESIGN: Prospective national surveillance study. METHODS: Measurement of relative trends in demographic, clinical and microbiological characteristics of tuberculosis cases reported in England between 1999 and 2003. RESULTS: Between 1999 and 2003, the number of tuberculosis cases reported in England increased by 19% from 5539 to 6608. Significant increases in tuberculosis cases were seen in the non-UK-born population who were recent entrants to the UK (arrival less than 5 years prior to diagnosis) relative to cases in the UK-born population, both in London [1.08; 95% confidence interval (CI) 1.02-1.14] and outside London (1.22; 95% CI 1.16-1.28). Cases of tuberculosis co-infected with human immunodeficiency virus (HIV) increased significantly both in London (1.19; 95% CI 1.12-1.27) and outside London (1.22; 95% CI 1.12-1.33) relative to cases not known to be co-infected with HIV. Small increases in the number of cases living in less-deprived areas were observed relative to those in the most-deprived areas (1.11; 95% CI 1.02-1.21) in London. The number of cases of isoniazid-resistant (1.09; 95% CI 1.02-1.16) and multi-drug-resistant tuberculosis (1.22; 95% CI 1.02-1.45) increased relative to drug-susceptible cases in London. CONCLUSIONS: Tuberculosis remains strongly associated with deprivation, but no real change in the distribution of tuberculosis cases by deprivation was observed over the study period. The proportion of tuberculosis cases co-infected with HIV has increased, but migration explains most of the recent trends in tuberculosis in England. Measures that target latent tuberculosis infection could have an increased role to play alongside measures against active disease in reducing the incidence of tuberculosis in the UK.