In Guadeloupe, the incidence of tuberculosis decreased between 1994 and 2000. The rate of resistance to at least one antibiotic remained constant at 11%, whereas the rate of multiple-drug resistance increased from 0.9 to 2.4% in 2000. The proportion of patients of foreign origin (mainly from Haiti and the Dominican Republic) increased whereas the number of French patients decreased. These results show that the epidemiology of tuberculosis in Guadeloupe is similar to industrialized countries as older people, foreigners from countries where TB is endemic, and HIV+ patients are at a higher risk to declare tuberculosis disease. Molecular typing realized by spoligotyping showed the importance of previous successive colonizations and migrations as characterized by the presence of major phylogenetic families originating essentially from Northern Europe (Haarlem), Latin America and Mediterranean (LAM) and from Anglo-Saxon countries (X). The sub-typing of clustered strains by IS6110-RFLP and by a PCR method based on the variable number of tandem DNA repeats (VNTR), highlighted 29 clusters, corresponding to 44.8% of clustered strains, and allowed to estimate the rate of recent transmission at 32.2%. The epidemiologic data associated with fingerprinting results underlined the importance of reactivation cases among older people, a significant number of imported TB cases without evident links, and casual contacts.