Introduction: The 2021 AHA/ACC Chest Pain Guideline classifies the likelihood of ischemia according to chest symptom characteristics. However, the associations of various chest symptoms with long-term risk of different cardiovascular disease (CVD) have not been fully investigated. Aim: To quantify the associations of chest pain and dyspnea with incident major CVD. Methods: In 13,200 ARIC participants (mean age 54 [SD 6] years, 56% female, 25% Blacks) without prior CVD at visit 1 (1987-89), we categorized chest pain into definite angina, possible angina, non-anginal chest pain, and no chest pain based on the WHO Rose questionnaire, and dyspnea into grade 0, 1, 2, and 3-4 based on the Medical Research Council scale. CVD outcomes included myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and ischemic stroke (median follow-up, 26-28 years). We estimated 30-year cumulative incidence accounting for competing risk of deaths and ran multivariable Cox models. Results: Definite angina and possible angina were robustly associated with incident MI (Table), with adjusted HR 1.83 (95%CI 1.51-2.22) and 1.64 (1.26-2.13), respectively. These two chest pain types were also related to HF, AF, and ischemic stroke, although possible angina did not reach statistical significance for stroke. Even non-anginal chest pain was associated with MI, HF, and AF. Dyspnea showed graded association with all CVD outcomes, but particularly with MI and HF (bottom half of Table). For example, grade 3-4 and 2 showed HR of 2.13 (1.71-2.65) and 1.41 (1.13-1.76), respectively, for MI. When chest pain and dyspnea were modeled simultaneously, their associations were independent. Conclusions: In persons without prior CVD, chest pain and dyspnea were independently associated with different CVD events over 30 years. Our findings suggest broad prognostic implications of chest pain beyond coronary disease and emphasize the importance of recognizing dyspnea for CVD risk management.