Epidemiological and clinical studies have consistently reported associations between smoking and posttraumatic stress disorder (PTSD). This study analyzed diagnostic interview data on 6,744 members of the Vietnam Era Twin Registry to clarify the PTSD-smoking relation and to examine whether genetic liability for smoking moderated this relation. Preexisting active (unremitted) PTSD increased risk of late-onset daily smoking. Remitted PTSD decreased risk. Active PTSD increased risk of smoking at all levels of genetic liability; the effect was strongest for those with least genetic liability. This suggests PTSD represents a nongenetic pathway to late-onset smoking among individuals who were nonsmokers prior to developing PTSD. If replicated, these results identify PTSD as a risk factor for smoking that should lead to early tobacco control treatment in this population.