Posttraumatic stress disorder (PTSD) frequently co-occurs with panic spectrum problems. Relatively little empirical work has tested possible mechanisms accounting for this association. Nicotine dependence often ensues subsequent to PTSD onset and research suggests smoking high numbers of cigarettes daily may lead to panic problems. The current study tested the hypotheses that nicotine dependence partially mediates the relations between PTSD and both panic attacks and panic disorder within a nationally representative sample of 5,692 (3,020 women; MAge = 45, SD = 18) adults from the National Comorbidity Survey–Replication. Results were consistent with hypotheses. These findings support the theory suggesting smoking among people with PTSD may be involved in the development of panic problems.