Background: The main aims of this cohort study were to measure the intrafamilial risk of transmission, sharing and stability of the most virulent S. mutans genotypes. Material and Methods: A total of 392 clinical isolates of S. mutans obtained from caries-active adults and genotyped to evaluate their transmissibility over time. After extraction of the chromosomal DNA, PCR were performed to detect the genes involved in the production of GbpA (gbpA) and mutacin types I, II, III and IV (mutAI, mutAII, mutAIII and mutAIV). Results: The gbpA, mutAI, mutAII, mutAIII and mutAIV genes were detected in 77.3, 12.5, 51, 16.6 and 89.8% of S. mutans isolates, respectively. The virulence of S. mutans was associated with its transmission (P < 0.01) and stability (P = 0.01), with the most virulent genotypes having higher transmissibility (RR = 1.83, 95% CI 1.44 to 2.32) and higher stability in the oral cavity (RR = 1.52, 95% CI 1.06 to 2.19). Conclusions: Genotypes with the genetic information to synthesize GbpA and mutacins present an important ecological advantage in the process of colonization by S. mutans; they remain stable among the oral microbiota of the host and favor intrafamilial transmission.