ObjectiveUnregulated stimulant use is rising globally, though trends in use of cocaine and crystal methamphetamine (CM), the two most commonly used unregulated stimulants in North America, are poorly characterized in many settings. In this study we examined patterns and associations between the injection of cocaine and CM over time in an urban Canadian setting. MethodsThe study collected data from two prospective cohorts of people who inject drugs in Vancouver, Canada, between 2008 and 2018. We applied a time series analysis, using multivariable linear regression to detect relationships between reported CM and cocaine injection and year, controlling for covariates. The study used cross-correlation to evaluate the relative trajectories of each substance over time. ResultsAmong 2056 participants, per annum rates of reported injection cocaine use declined significantly over the duration of this study from 45 % to 18 % (p < 0.001), while rates of CM injection increased from 17 % to 32 % (p < 0.001). Multivariable linear regression showed that recent CM injection was negatively associated with recent cocaine injection (β = −0.609, 95 % CI = −0.750, −0.467). Cross-correlation demonstrated that injection CM use was associated with a decrease in the likelihood of cocaine injection 12 months later (p = 0.002). ConclusionsThese findings demonstrate an epidemiological shift in patterns of injection stimulant use, with rising CM injection associated with a corresponding decrease in cocaine injection over time. Strategies are urgently needed that help to treat and reduce harm among the growing population of people who inject CM.