Background: In Canada, many patients face substantial out-of-pocket costs for prescription medication, which may affect their ability to take their medications as prescribed. We sought to conduct a comprehensive analysis of the burden and predictors of cost-related nonadherence in Canada. Methods: Using pooled data from the 2015, 2016, 2018, 2019, and 2020 iterations of the Canadian Community Health Survey, we calculated weighted population estimates of the burden of cost-related nonadherence in the preceding 12 months and used logistic regression models to measure the association of 15 demographic, health, and health system predictors of cost-related nonadherence overall and stratified by sex. Results: We included 223 085 respondents. We found that 4.9% of respondents aged 12 years or older reported cost-related nonadherence. Those who self-identified as female, belonging to a racial or ethnic minority group, or bisexual, pansexual, or questioning were more likely to report cost-related nonadherence. Younger age, higher disease burden, poorer health, non-employer prescription drug coverage, and not living in the province of Quebec were associated with cost-related nonadherence. Interpretation: Our nationally representative findings reveal inequities that disproportionally affect marginalized people at the intersections of sex, race, age, and disability, and vary by province. This foundational understanding of the state of cost-related nonadherence may be used to inform potential expansion of public drug coverage eligibility, premiums, and cost-sharing policies that address financial barriers to medication adherence. [See related editorial at www.cmaj.ca/lookup/doi/10.1503/cmaj.241650][1] [1]: /lookup/volpage/196/E1347