Objective: This study explored factors associated with public stigma toward individuals misusing alcohol in Mexico. Methods: A randomized experimental vignette methodology was used to assess multiple domains of substance use-related stigma and their relationship to the gender of the vignette subject and the sociodemographic characteristics of respondents. Results: Although levels of stigma toward women who were misusing alcohol did not differ significantly from stigma toward men misusing alcohol, stigma levels and type of stigma reported varied with the sociodemographic characteristics of respondents. Education level, gender, self-stigma and openness to seeking mental health services were differentially associated with the three stigma domains. Conclusions: Accordingly, targeted community based stigma reduction efforts are needed to decrease stigma toward those misusing alcohol, and to support treatment initiation, ongoing treatment engagement and long term recovery efforts. Suggestions for future research on the relationship between substance use and stigma are offered.