If Mycobacterium tuberculosis isolates from 2 people have the same genotype, transmission may have occurred between them. Genotyping based on the insertion sequence IS6110 uses identical restriction fragment length polymorphisms ("fingerprints") to infer transmission. However, once transmission has occurred, the genotypes may mutate, resulting in divergent fingerprints. Estimation of the proportion of tuberculosis (TB) cases due to recent transmission includes 3 approaches to determine if genotypes match: exact matching (assumes no fingerprint change); band-addition, band-loss, band-shift matching (ad hoc attempt to account for fingerprint changes); and genetic distance (directly accounts for fingerprint changes). Via simulation study, the authors varied the fingerprint change rate, level of recent transmission, and background genetic heterogeneity and estimated sensitivity, specificity, and bias of the recent transmission index by matching method. For exact matching, specificity was always high, but sensitivity decreased as the change rate increased. For band-addition, band-loss, band-shift matching, specificity decreased as genetic diversity decreased, and sensitivity remained high as the change rate increased. Genetic distance offered a compromise between the 2. Results from this study suggest that interpretation of the recent transmission index and the resulting necessary public health interventions will vary according to how researchers account for spontaneous mutation when estimating transmission from genotyping data.