Objective: Research examining the responders of the World Trade Center terrorist attacks of 9/11 has found that Hispanic responders are at greater risk for posttraumatic stress disorder (PTSD) than non-Hispanic White responders. However, no studies have examined how acculturation may influence the relationship between coping and PTSD in Hispanic 9/11 responders. This novel study is the first to examine differences in coping and PTSD among Hispanic responders by level of acculturation. Methods: The sample is composed of 845 Hispanic 9/11 responders who were seen at the World Trade Center Health Program and participated in a web-based survey. Using logistic and multiple linear regression, we examined how acculturation is related to their coping strategies and risk for PTSD. We also tested for interaction to examine whether level of acculturation moderated the relationship between coping and PTSD symptom severity. Results: Key findings revealed that higher acculturation is associated with the use of substances, venting, and humor to cope, while lower acculturation is associated with the use of active coping and self-distraction in this sample. We also found that less acculturated responders were more likely to experience more severe PTSD. Lastly, our findings revealed that Hispanics who are more acculturated and used substances to cope had more severe PTSD than less acculturated responders. Conclusion: These findings highlight the need to consider the role of acculturation in Hispanic responders' coping and PTSD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).