Because exposure to potentially traumatic events is common (Kessler, Sonnega, Bromet, & Hughes, 1995), the mechanisms through which post-traumatic stress disorder (PTSD) symptoms develop is a critical area of investigation (Ozer, Best, Lipsey, & Weiss, 2003). Among the mechanisms that may predict PTSD symptoms is spiritual struggle, a set of negative religious cognitions related to understanding or responding to stressful events. Although prominent theories emphasize cognitive factors in the development and maintenance of PTSD symptoms, they have not explicitly addressed spiritual struggle. The present prospective study tested the role of spiritual struggle in the development and maintenance of PTSD symptoms following trauma. We assessed exposure to trauma and non-trauma events during the first year of college, spiritual struggle due to the most stressful event, and PTSD symptoms resulting from the index event. Spiritual struggle partially mediated the relationship between trauma and PTSD symptoms. Interestingly, some individual subscales of spiritual struggle (specifically, Punishing God Reappraisal, Reappraisal of God's Powers, and Spiritual Discontent) partially mediated the relationship between trauma and PTSD symptoms; however, reappraisal of the event to evil forces did not relate to PTSD symptoms. These results suggest that spiritual struggle is an important cognitive mechanism for many trauma victims and may have relevance for cognitive therapy for PTSD.