OBJECTIVES: To quantify incidence of tooth loss, prosthodontic dental restoration, and chewing difficulty onset and the effect of tooth loss and prosthodontic restoration on chewing difficulty onset. DESIGN: A prospective cohort study of oral health and related behaviors with in-person interviews and clinical examinations conducted at baseline and 24 months. Telephone interviews were conducted every 6 months between these sessions. SETTING: A community-based sample of four counties in north Florida. PARTICIPANTS: Eight hundred seventy-three persons who had at least one tooth and were aged 45 and older at baseline. MEASUREMENTS: Persons were queried regarding onset of chewing difficulty, an important component of oral health-related quality of life (OHRQoL). The chewing index of Leake, with minor revision, was the primary outcome of interest. Tooth loss was measured using direct clinical examination. Dental care use was reported during each interview. RESULTS: Approximately 22% of participants reported tooth loss during follow-up. Fixed prosthodontics (crowns and bridges) was the most common form of new prosthodontic treatment. People who reported tooth loss were 2.7 times more likely to report chewing difficulty onset than people without tooth loss (P<.001). Having fewer occluding pairs of teeth at baseline was significantly associated with an increased probability of chewing difficulty onset. People who received removable prosthodontic treatment were much less likely to report chewing difficulty onset than people who did not (P<.01). CONCLUSION: Incident tooth loss and removable prosthodontic restoration strongly predicted chewing difficulty, an important component of OHRQoL.