Objectives. To evaluate the impact of frequent cannabis use on injection cessation and injection relapse among people who inject drugs (PWID).Methods. Three prospective cohorts of PWID from Vancouver, Canada, provided the data for these analyses. We used extended Cox regression analysis with time-updated covariates to analyze the association between cannabis use and injection cessation and injection relapse.Results. Between 2005 and 2018, at-least-daily cannabis use was associated with swifter rates of injection cessation (adjusted hazard ratio [AHR] = 1.16; 95% confidence interval [CI] = 1.03, 1.30). A subanalysis revealed that this association was only significant for opioid injection cessation (AHR = 1.26; 95% CI = 1.12, 1.41). At-least-daily cannabis use was not significantly associated with injection relapse (AHR = 1.08; 95% CI = 0.95, 1.23).Conclusions. We observed that at-least-daily cannabis use was associated with a 16% increase in the hazard rate of injection cessation, and this effect was restricted to the cessation of injection opioids. This finding is encouraging given the uncertainty surrounding the impact of cannabis policies on PWID during the ongoing opioid overdose crisis in many settings in the United States and Canada. (Am J Public Health. Published online ahead of print August 20, 2020: e1-e8. doi:10.2105/AJPH.2020.305825).