We conducted a retrospective, population-based study with use of restriction fragment length polymorphism (RFLP) analysis to determine the incidence of and risk factors for clustering of Mycobacterium tuberculosis isolates, indicative of recently transmitted infection, among patients with culture-proven tuberculosis diagnosed between 1 July 1992 and 1 January 1995 in Amsterdam. We found that 214 (47%) of 459 patients were in 53 clusters, probably because of recent transmission of M. tuberculosis among 161 (35%) of these patients. Conventional contact tracing resulted in identification of 5.6% of the 161 patients. Clustering was more frequent among Dutch patients (59.3%) than among foreign ethnic patients (42.1%) (P = .002). The independent risk factor for clustering among Dutch patients was younger age; the independent risk factors among foreign ethnic patients were hard-drug use; alcohol abuse; and country of origin (Surinam or the Netherlands Antilles). These findings suggest the shortcomings of the usual tuberculosis control policies in Amsterdam. We identified several risk factors for clustering, which may guide adjustment of tuberculosis control and contact tracing strategies.