Background: Homocysteine (Hcy) has been associated with several health problems, including reduced physical capacity. No study appears to have looked at the role of Hcy values longitudinally on physical capacity deterioration in older adults. The objective is to examine cross-sectional and prospective associations between Hcy values and frailty in the elderly and investigate Hcy potential association with the onset of frailty. Methods: 769 community-dwelling older adults from the MAPT study were recruited for this study. Total Hcy was measured at baseline. Frailty was evaluated at 5 different collection timepoints: baseline, 6-month, 1-, 2-, and 3year using a frailty index (FI) composed of 19 items. Linear regressions adjusted for all the confounders (age, gender, educational level, MAPT group allocation and Omega-3) were performed to examine the cross-sectional associations of homocysteine values with the FI. A cox model was used to test the association of Hcy with the onset of frailty. Results: Mean Hcy values (15.9 ± 5.6 μmol\L) were obtained from 769 community-dwelling adults (75.7 ± 4.6 years old). After adjustments, a significant (β = 0.002, (00002-0.003)) and positive association between baseline Hcy values and FI was found (ß = 0.002). Additionally, higher values of Hcy were associated with a worsening of FI after 3 years (ß = 0.002, p = 0.003). A significant association between baseline Hcy values and the likelihood of developing frailty was discovered by incident event analysis (HR: 1.04 (1.01-1.06), p = 0.004). Conclusion: High levels of Hcy are associated with the fragility process in community-dwelling older adults.