We assessed associations between new-onset (post-September 11, 2001 [9/11]) lower respiratory symptoms reported on 2 surveys, administered 3 years apart, and acute and chronic 9/11-related exposures among New York City World Trade Center-area residents and workers enrolled in the World Trade Center Health Registry. World Trade Center-area residents and workers were categorized as case participants or control participants on the basis of lower respiratory symptoms reported in surveys administered 2 to 3 and 5 to 6 years after 9/11. We created composite exposure scales after principal components analyses of detailed exposure histories obtained during face-to-face interviews. We used multivariate logistic regression models to determine associations between lower respiratory symptoms and composite exposure scales. Both acute and chronic exposures to the events of 9/11 were independently associated, often in a dose-dependent manner, with lower respiratory symptoms among individuals who lived and worked in the area of the World Trade Center. Study findings argue for detailed assessments of exposure during and after events in the future from which potentially toxic materials may be released and for rapid interventions to minimize exposures and screen for potential adverse health effects.