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OBJECTIVE: The authors sought to determine the relationship of panic attacks, cigarette smoking, and neuroticism. METHOD: Data were drawn from the Midlife Development in the United States Survey, a representative household survey of the adult population of the United States (N=3,032). Multivariate logistic regression analyses were used to determine the association between panic attacks and cigarette smoking and to determine whether neuroticism was an independent predictor of the co-occurrence of cigarette smoking and panic attacks. RESULTS: The majority of individuals with panic attacks had been regular smokers during their lifetime (81.1%), a significantly higher rate than seen among subjects without panic attacks (69.4%). Regular cigarette smoking was associated with a significantly greater risk of current panic attacks. This significant association persisted after analyses controlled for demographic characteristics, depression, and alcohol/substance use disorders but was no longer evident after analyses adjusted for neuroticism. Neuroticism independently predicted the co-occurrence of regular cigarette smoking and panic attacks but did not predict either panic attacks or cigarette smoking in the absence of the other. CONCLUSIONS: Consistent with previous findings, these data suggest that panic attacks are associated with greater risk of cigarette smoking but provide new evidence that neuroticism may play an essential role in this relationship. These data are preliminary but, if replicated, suggest that neuroticism may reflect a shared vulnerability for the co-occurrence of cigarette smoking and panic attacks. Future studies are needed to further explore the mechanism of this association.