Difficulty tolerating distress (e.g., distress tolerance [DT]) and regulating emotions (e.g., emotion regulation [ER]) are implicated as transdiagnostic risk factors for various internalizing disorders. The present study investigated the relationships among six internalizing disorder symptoms, baseline ER, and DT in college students ( N = 137) to identify which internalizing disorders were most closely associated with DT. We expected ER and internalizing symptoms to be associated with DT and that ER would moderate relationships among internalizing symptoms and both trait DT and state distress. Results indicated that ER, Post-traumatic Stress Disorder (PTSD), and social anxiety symptoms influenced trait DT. ER moderated the associations between depression, anxiety, and panic disorder (PD) symptoms, and trait DT at the .05 level. Similarly, ER moderated the association between PD symptoms and anticipatory distress at the .05 level. However, these analyses did not withstand the Bonferroni adjustment ( p = .008) for multiple comparisons. Findings suggest that, when considering transdiagnostic symptoms, certain internalizing symptoms (i.e., social anxiety, PTSD) may have a stronger influence on trait DT. Further, strong ER abilities may buffer the adverse effects of internalizing symptoms on one’s perceived ability to handle distress. These patterns may not translate to individuals’ behavioral capacity to handle distress.