The current study examined the role of World Trade Center (WTC) disaster exposure (hours spent working on the site, dust cloud exposure, and losing friend/loved one) in exacerbating the effects of post-disaster life stress on posttraumatic stress disorder (PTSD) symptoms and overall functioning among WTC responders. Participants were 18,896 responders (8466 police officers and 10,430 non-traditional responders) participating in the WTC Health Program who completed an initial examination between July, 2002 and April, 2010 and were reassessed an average of two years later. Among police responders, there was a significant interaction, such that the effect of post-disaster life stress on later PTSD symptoms and overall functioning was stronger among police responders who had greater WTC disaster exposure (β's = .029 and .054, respectively, for PTSD symptoms and overall functioning). This moderating effect was absent in non-traditional responders. Across both groups, post-disaster life stress also consistently was related to the dependent variables in a more robust manner than WTC exposure. The present findings suggest that WTC exposure may compound post-disaster life stress, thereby resulting in a more chronic course of PTSD symptoms and reduced functioning among police responders.