Orofacial pain is often persistent, but it is not clear why it lasts in some patients but not in others. We aimed to describe the natural course of orofacial pain in a general population sample over a four-year period and to identify factors that would predict the persistence of pain. A cross-sectional population-based survey was conducted in the United Kingdom, involving 2504 participants (participation rate 74%), of whom 646 (26%) reported orofacial pain. Overall, 424 (79% adjusted participation rate) of these individuals participated at the four-year follow-up, of whom 229 (54%) reported orofacial pain and 195 (46%) did not report such pain. Persistent orofacial pain was associated with females, older age, psychological distress, widespread body pain, and taking medication for orofacial pain at baseline. These findings may have implications for the identification and treatment of patients with orofacial pain.