The aim of this study was to investigate the relationship between participants' sociodemographic characteristics and the degree to which they stigmatize people with an opioid addiction. A randomized, between-subjects case vignette study (n = 2605) was conducted with a nationwide online survey. We investigated how the stigmatization toward a hypothetical individual who misused prescription opioids differed across participants' sociodemographic factors (ie, age, gender, education, race, and income). Our results showed that study participants who were male, white, low-income, college graduates, and younger rated the hypothetical individual with an opioid addiction with lower stigma. In addition, we showed that participant gender moderated the relationship between information given about initiation of opioid use (received prescription opioids from a doctor vs took prescription opioids from a friend) and opioid stigma perceptions. Our results support previous findings that stigmatizing attitudes towards drug use vary across participant sociodemographic characteristics. The findings from our study provide a better understanding of how stigmatizing attitudes towards prescription opioid use differ across sociodemographic characteristics and can serve to improve negative perceptions of those with an opioid addiction.