Hyperhomocysteinemia (HHCYS) has been associated with systolic heart failure. However, it is still unknown that serum homocycsteine level was useful in predicting the outcome in patients with diastolic dysfunction. We conducted a cohort study to determine if HHCYS was associated with poor prognosis in diastolic dysfunction patients. The Chin-Shan Community Cardiovascular Cohort (CCCC) study was designated to investigate the trends of cardiovascular morbidity and mortality in a community. Individuals who were 35 years and above were enrolled. Participants were categorized by homocysteine concentration quartiles. We used multivariate Cox proportional hazards models to calculate the hazard ratio (HR) of the 4th quartiles versus the 1st quartile. Area under the receiver-operating characteristic (ROC) curve was to compare prediction measures. A total of 2020 participants had completed the echocardiography examination, and 231 individuals were diagnosed as diastolic dysfunction. A total 75 participants had died during follow-up period. HHCYS was found to be significantly associated with poor prognosis. The adjusted HR for homocysteine level was 1.07 (95% confidence interval [CI], 1.01-1.14). Participants in the highest quartile had a 1.90 (95% CI, 0.88-4.12, P for trend, .026) fold risk for all cause death, compared with those in the lowest quartiles. The HR was 1.88 (95% CI, 1.07-3.29) using 11.11 mu mol/L as cut point for hyperhomocysteine. HHCYS was significantly associated with poor prognosis in diastolic dysfunction participants in the community.