BackgroundIn Canada, substance use is one of the key predisposing factors that may lead to risky sexual behaviors among post-secondary students. There is considerable economic burden and significant public health concern posed by substance use and sexually transmitted infections (STIs). The purpose of this study was to examine the prevalence of substance use preferences (alcohol, cannabis, and other drugs) and its association with STIs among Canadian post-secondary students.Materials and methodsThis is a cross-sectional study using data from the National College Health Assessment II, Spring 2016 survey conducted by the American College Health Association. There were 31,642 sexually active participants, representing 41 post-secondary institutions in Canada. Descriptive analysis and logistic regression were conducted to estimate the effect of substance use preferences on STIs.ResultsThis study found that participants reported being current users of alcohol (80%), cannabis (23%), and other drugs (8%). Additionally, 3.96% of the participants self-reported being diagnosed or treated for an STI in the last 12 months. Multivariate logistic analysis revealed current cannabis use to be significantly associated with self-reported STIs (aOR, 1.34; 95% CI, 1.12–1.6). There was a significant association between current drug use and STIs among male (aOR, 3.04; 95% CI, 2.27–4.06) and female participants (aOR, 1.87; 95% CI, 1.52–2.30). Having multiple sexual partners, a history of sexual assault, being homosexual, Black, and >21 years old were also found to have a significant association with self-reported STIs (P-value <0.001).ConclusionIn this study, significant associations were found between cannabis and other drug use and STIs among post-secondary students in Canada. The results of this study can help inform institutions of higher learning and public health professionals in the design, implementation, and evaluation of substance use and STI policies and effective school-based health programming.