Marks C, Borquez A, Jain S, et al. - Considering the data indicating the association of opioid agonist treatment (OAT) enrollment with a reduced likelihood of assisting with injection drug use (IDU) initiation and that the majority of IDU initiations are assisted by people who inject drugs (PWID), researchers here examined how recent OAT enrollment influence assisting IDU initiation across several North American settings. Further, they sought to project the potential population-level impact of OAT scale-up within the PWID population on IDU initiation using dynamic modeling. A prospective multicohort study of PWID in 3 settings (Vancouver, Canada [n = 1,737]; San Diego, United States [n = 346]; and Tijuana, Mexico [n = 532]) from 2014 to 2017 was used to extract data for this work. The analysis revealed an association of past–6-month enrollment in OAT with nearly half the likelihood of past–6-month provision of assistance with IDU initiation. A dynamic model of IDU initiation was parameterized using these associations, and the population-level influence of scaling up OAT coverage on IDU initiations over the next decade was estimated in a generic North American setting. It is estimated that scaling up of OAT coverage from approximately 21% to 60% among PWID may decrease the number of people who initiate IDU each year by 23% after a decade. This suggests that improving OAT coverage among PWID can have an important influence on reducing IDU initiations in addition to its known advantages of preventing HIV, hepatitis C virus, and overdose among PWID.