Aims: To investigate whether pain catastrophizing has not only direct effects as a predictor of pain-related interference but also indirect effects as a mediator in the relationship between psychological distress and pain interference and to examine the mediating roles of subtypes of catastrophizing (magnification, rumination, and helplessness) between psychological distress and interference. Methods: This retrospective study included 815 patients with orofacial pain aged 18 to 81 years. All participants completed a set of self-administered questionnaires concerning pain interference (Brief Pain Inventory), psychological distress (Symptom Checklist-90-Revised), and pain catastrophizing (Pain Catastrophizing Scale) at the first consultation. The associations between these three variables were calculated using mediation path analysis. Results: Pain catastrophizing predicted pain interference. In addition, 34% of the variance in pain interference attributable to psychological distress was mediated by catastrophizing when controlling for pain duration and severity. The greatest portion of the mediating effect of catastrophizing was attributable to the helplessness component. Conclusion: Within the limitations of cross-sectional studies, this study demonstrated that pain catastrophizing mediates the effects of psychological distress on pain interference in patients with orofacial pain. Most of the mediating effects were attributable to the helplessness component of pain catastrophizing. Cognitive behavioral therapy targeting pain catastrophizing, specifically helplessness, could potentially reduce pain-related disability in orofacial pain patients. Keywords: mediation analysis, orofacial pain, pain catastrophizing, pain interference, psychological distress