OBJECTIVE: To describe management and outcome of tuberculosis (TB) and current practices for isolation in two urban hospitals in the Midwest. DESIGN: Retrospective cohort study. SETTING: Barnes Hospital and Jewish Hospital, tertiary-care and community hospitals affiliated with Washington University School of Medicine in St Louis, Missouri. PATIENTS: All adult patients with a positive culture for Mycobacterium tuberculosis from 1988 to 1994. RESULTS: We identified 122 cases at Barnes and Jewish Hospitals (36.5/100,000 hospital discharges), median age was 59.0 years, 61.5% were non-Caucasian, and 54.9% resided within the city limits. Underlying risk conditions were common: substance abuse (25%), recent TB contact (24%), and foreign birth (13%). Coexistent human immunodeficiency virus infection (8%) was uncommon. Of skin-tested cases, 22% were anergic; of the rest, 22% tested negative. Almost 20% of cases had prior positive skin tests, and thus were preventable, but had not received adequate prophylaxis. Of hospitalized patients with pulmonary TB, 70% received respiratory isolation. Antibiotic resistance was recognized in 16%; only 19% of cases initially received four-drug therapy. TB-related death occurred in 16%. CONCLUSIONS: In this area, TB cases primarily involve traditional risk groups without HIV coinfection. Current infection control practices, diagnostic strategies, and initial treatment regimens are suboptimal. Education about local disease epidemiology is needed to prevent nosocomial TB transmission.