Prisons play a significant role in the epidemiology of drug-resistant tuberculosis. A total of 114 Mycobacterium tuberculosis isolates recovered from patients in the Archangel prison (Archangel, Russia) in 2001 were studied using restriction fragment-length polymorphism analysis and spoligotyping. Drug susceptibility was analyzed by the radiometric broth method (BACTEC; Becton Dickinson Diagnostic Systems). According to genotyping studies, 87 (76.3%) of the isolates belonged to the W-Beijing family. Nearly all (96.6%) W-Beijing isolates were part of a cluster, whereas only 25.9% of the other isolates were clustered (P < .001). The largest cluster comprised 43 patients. Multidrug resistance was high among new (34.0%) and previously treated (55.0%) cases. Resistance to ethambutol (OR, 3.4; 95% CI, 1.0–12.7; P = .03) and streptomycin (OR, 4.2; 95% CI, 1.5–11.6; P = .001) was significantly associated with infection with W-Beijing isolates. Tuberculosis due to drug-resistant W-Beijing isolates is a major problem in the Archangel prison.