Olivier and Prevots discuss Gross and colleagues's report of a retrospective study, HALT-NTM (Healthcare-associated Links in Transmission of NTM; NCT04024423), that used whole-genome sequencing (WGS) and a systematic, evidence-based, standardized epidemiologic approach to investigate the potential for transmission versus environmental acquisition at the University of Colorado Adult CF Center. Core genome analysis identified 11 clusters comprising 27 subjects, with 4 of these clusters (2 Mycobacterium abscessus and 2 Mycobacterium avium) having overlapping opportunities for healthcare transmission. This study does make a significant contribution to the building literature seeking to address nontuberculous mycobacteria (NTM) transmission and acquisition. One of the most promising aspects is its planned extrapolation to other cystic fibrosis (CF) centers, which is already underway using a standardized study design. With increasing numbers of same-site clusters being evaluated in a similar fashion at multiple geographically dispersed centers with variations in infection control practices, additional data may help to clarify the validity of the findings in this study.