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Drug abuse and addiction exist around the world. People addicted to drugs such as opium or heroin often encounter dehumanizing discriminatory behaviors and health-care systems that are reluctant to provide services. Experiencing discrimination often serves as a barrier to receiving help or finding a home or work. Therefore, it is important to better understand the mechanisms that lead to the stigmatization of drug addiction and who is more prone to stigmatizing behaviors. There is also a dearth of research on whether different patterns of stigma exist in men and women. Therefore, this study investigated factors affecting gender-specific stigmatization in the context of drug addiction. In our vignette study (<em>N</em><sub><em>Mensample</em></sub>= 320 and<em>N</em><sub><em>Womensample</em></sub>= 320) in Iran, we experimentally varied signals and signaling events regarding a person with drug addiction (i.e.,<em>N</em><sub><em>Vignettes</em></sub>= 32 per sample), based on Attribution Theory, before assessing stigmatizing cognitions (e.g., blameworthiness), affective responses (e.g., anger), and discriminatory inclinations (e.g., segregation) with the Attribution Questionnaire. We also tested assumptions from the Familiarity Hypothesis by assessing indicators of respondents' familiarity with drug addiction (e.g., knowledge about addiction). Results, for example, show higher stigma if the person used “harder” drugs, displayed aggressive behavior, or had a less controllable drug urge. Self-attributed knowledge about addiction or prior drug use increased some forms of stigma, but diminished others. These findings only partially converged between men and women. We suggest that anti-stigma initiatives should consider information about the stigmatized person, conditions of the addiction, and characteristics of stigmatizers.