The purpose of this study was to determine the extent of transmission of tuberculosis in a large prison population over an 18-mo period. Restriction-fragment-length polymorphism (RFLP) analysis of isolates of Mycobacterium tuberculosis was performed, using the insertion sequence IS6110 and the plasmid pTBN12. Patients infected with strains having the same fingerprint were grouped in clusters. Medical records were reviewed and movement of inmates among prisons was examined for selected patients. Tuberculosis was diagnosed in 216 inmates (case rate = 2,283 per 100,000 per year). Isolates from 210 (97%) patients were fingerprinted, 155 (74%) were grouped in 25 clusters, and 55 (26%) showed a unique fingerprint. Recent infection was inferred in 62% of these patients. Eighty-four percent (161 of 192) of patients tested were human immunodeficiency virus (HIV)-positive, of whom 121 were in clusters and 40 were not (p = 0.74). Patients in clusters were less adherent with tuberculosis treatment than those not in clusters (p < 0.05), and prison transmission of resistant strains was observed. It is crucial that infection control guidelines be fully implemented in the prison setting to prevent tuberculosis transmission.