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Objective: To systematically examine the content of opioid-related advertisements., Design: Content analysis and quantitative assessment., Setting: North America., Participants: Researchers examined advertisements in 2 issues per year from 1996 to 2016 of American Family Physician, Canadian Family Physician , the Canadian Medical Association Journal, JAMA , and the New England Journal of Medicine ., Main Outcome Measures: Number of advertisements, nature of the claims made, and quality of cited evidence in the advertisements., Results: Opioid advertisements composed 89 of the 3173 pharmaceutical advertisements in 210 journal issues searched. Seventy-three advertisements were able to be obtained for analysis. Thirty-four (46.6%) did not mention the addictive potential of opioids, and 54 of 73 (74.0%) did not mention the possibility of death. All referenced studies in advertisements were funded by pharmaceutical organizations or had pharmaceutical company employees as authors. No advertisements cited high-quality evidence., Conclusion: Many claims of the effectiveness and safety of opioids were published in medical journals through advertisements. Advertisements did not usually mention key negative information about opioids. Although the extent to which these advertisements directly influenced the development of the opioid crisis in North America is unknown, the marked omission of important detrimental effects of opioids may have played a role. Further efforts to restrict opioid marketing may be warranted., (Copyright © 2023 the College of Family Physicians of Canada.)