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Introduction: Dental health problems such as tooth loss are related to inflammation and detrimental dietary changes, and may be linked to elevated risks of future heart disease. Most previous studies only investigated pre-existing tooth loss at baseline; hence, whether incident (more recent and later in life) tooth loss is associated with an increased risk of future coronary heart disease (CHD) remains unclear.Hypothesis: We prospectively investigated how recent tooth loss was associated with subsequent risk of CHD in middle-aged adults.Methods: This prospective study included women from the Nurses’ Health Study (NHS) and men from the Health Professionals Follow-Up Study (HPFS) who were initially free of CHD and cancer. Participants were asked about the number of natural teeth first in 1986 in the HPFS, and in 1992 in the NHS. On follow-up questionnaires, participants reported whether they had any recent tooth loss. We calculated cumulative tooth loss during an 8-year assessment period (1992-2000 in the NHS; 1986-1998 in the HPFS) among participants aged 45-69 y. Hazard ratios (HRs) for the incidence of CHD (fatal CHD or non-fatal MI) were examined across categories of the number of tooth loss (none, 1 loss, and 2 or more loss). Follow-up time was calculated after the assessment of tooth loss until the end of follow-up in 2012. We examined risks of CHD separately among individuals with 25-32 natural teeth at the initial examination (n=41939, among whom 1754 incident cases of CHD accrued during 540,744 person-years of follow-up), as well as among all eligible participants (n=60967, among whom 2440 incident cases of CHD accrued during 760,351 person-years of follow-up).Results: Among participants with 25-32 natural teeth at baseline, men and women who lost 2 or more teeth had a significantly increased risk of CHD (Pooled: HR 1.23; 95% CI: 1.06, 1.42) as compared to those with no tooth loss, after adjustment for hypertension, dyslipidemia, diabetes, dietary habits (including the Alternative Healthy Eating Index (AHEI) score, alcohol, multivitamin supplement use), lifestyle and demographic factors. The association was also independent of concurrent changes (during the same period of tooth loss assessment) in AHEI score, physical activity, body weight, and status of hypertension, dyslipidemia, and diabetes (pooled HR 1.22, 95% CI: 1.06, 1.41). When we examined the risk of CHD among all the eligible participants, greater loss of teeth (2 or more loss vs. no loss: pooled HR: 1.16; 95% CI: 1.04, 1.30) and having fewer natural teeth (less than 17 vs. 25-32 teeth: pooled HR: 1.25; 95% CI: 1.08, 1.46) were independently and significantly associated with increased risk of CHD.Conclusions: Our results suggest that among middle-aged adults, a higher number of teeth lost in the recent past may be associated with subsequent risk of CHD, independent of the baseline number of natural teeth and traditional risk factors.