Using restriction fragment-length polymorphism data, we conducted a retrospective cohort study of 139 adult patients with pulmonary tuberculosis to investigate the clinical impact of Mycobacterium tuberculosis infection with a clustered isolate. The cumulative all-cause mortality rate during treatment was 21%. Patients with clustered DNA fingerprint patterns had a reduced risk of death, compared with patients with unique patterns (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.2-1.1), but this finding was confounded by age (adjusted HR, 0.8; 95% CI, 0.4-1.8). After adjustment for age, the strongest predictors of death were such underlying illnesses as diabetes mellitus, renal failure, chronic obstructive pulmonary disease, and human immunodeficiency virus infection. We conclude that comorbidity and immunosuppression are important predictors of survival for patients with pulmonary tuberculosis in an inner-city cohort. Recently transmitted infection, as determined by use of DNA fingerprinting to classify patients' isolates as being either clustered or unique, was not independently associated with death.