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To examine the nature and impact of smoking stigma, we developed the Internalized Stigma of Smoking Inventory (ISSI), tested its validity and reliability, and explored factors that may contribute to smoking stigma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the ISSI in a sample of smokers with mental health diagnoses (<jats:italic>N<\/jats:italic>\u2009=\u2009956), using exploratory and confirmatory factor analysis, and assessed construct validity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Results reduced the ISSI to eight items with three subscales: smoking <jats:italic>self\u2010stigma<\/jats:italic> related to shame, <jats:italic>felt stigma<\/jats:italic> related to social isolation, and <jats:italic>discrimination<\/jats:italic> experiences. Discrimination was the most commonly endorsed of the three subscales. A multivariate generalized linear model predicted 21\u201330% of the variance in the smoking stigma subscales. Self\u2010stigma was greatest among those intending to quit; felt stigma was highest among those experiencing stigma in other domains, namely ethnicity and mental illness\u2010based; and smoking\u2010related discrimination was highest among women, Caucasians, and those with more education.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and Conclusion<\/jats:title><jats:p>Smoking stigma may compound stigma experiences in other areas. Aspects of smoking stigma in the domains of shame, isolation, and discrimination were related to modeled stigma responses, particularly readiness to quit and cigarette addiction, and were found to be more salient for groups where tobacco use is least prevalent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Scientific Significance<\/jats:title><jats:p>The ISSI measure is useful for quantifying smoking\u2010related stigma in multiple domains. 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