Molecular genotyping of Mycobacterium tuberculosis has proved to be a powerful tool in tuberculosis surveillance, epidemiology, and control. Based on results obtained through 15 years of nationwide IS6110 restriction fragment length polymorphism (RFLP) genotyping of M. tuberculosis cases in Denmark, a country on the way toward tuberculosis elimination, we discuss M. tuberculosis transmission dynamics and point to areas for control interventions. Cases with 100% identical genotypes (RFLP patterns) were defined as clustered, and a cluster was defined as cases with an identical genotype. Of 4,601 included cases, corresponding to 76% of reported and 97% of culture-verified tuberculosis cases in the country, 56% were clustered, of which 69% were Danes. Generally, Danes were more often in large clusters (≥ 50 persons), older (mean age, 45 years), and male (male/female ratio, 2.5). Also, Danes had a higher cluster frequency within a 2-year observation window (60.8%), and higher clustering rate of new patterns over time, compared to immigrants. A dominant genotype, cluster 2, constituted 44% of all clustered and 35% of all genotyped cases. This cluster was primarily found among Danish males, 30 to 59 years of age, often socially marginalized, and with records of alcohol abuse. In Danes, cluster 2 alone was responsible for the high cluster frequency level. Immigrants had a higher incidence of clustered tuberculosis at a younger age (0 to 39 years). To achieve tuberculosis elimination in Denmark, high-risk transmission environments, like the cluster 2 environment in Danes, and specific transmission chains in immigrants in the capital area, e.g., homeless/socially marginalized Somalis/Greenlanders, often with alcohol abuse, must be targeted, including groups with a high risk of reactivation.