Objectives To investigate the relationship between frailty, metabolic syndrome (MetS), and loss of independence leading to the onset of disability or death among community-dwelling older Japanese.Methods Between 2002 and 2011, we conducted a 7-year prospective study involving 1,453 residents aged 65 years and over, initially free of disability, who underwent a comprehensive geriatric assessment in Kusatsu town. Statistical analysis was conducted for those with complete values, resulting in a variable number of subjects for each data point. Frailty was defined for 1,335 subjects as three or more of the following criteria: weight loss (>2-3 kg in the past six months), weakness (grip strength was <26 kg for men and <18 kg for women), exhaustion (answer of "no" to the question "Do you feel full of energy?" on the Geriatric Depression Scale), slowness (usual gait speed<1.0 m/s), and low physical activity (answer of "less than once a week" to the question "How often do you usually go outdoors?"). MetS was defined for 1,450 subjects from the Japanese definition. The Cox proportional-hazard regression model was used to estimate hazard ratio (HR) of loss of independence for 1,217 subjects.Results During the follow-up, 494 cases of loss of independence, including 376 disabilities and 118 deaths were identified. In men and women, the incidence of the loss of independence showed a significant linear trend according to the severity classification of frailty. By contrast, there was no relationship between MetS and the loss of independence. Subjects classified as prefrail and frail had an increased risk of loss of independence compared with robust participants, with sex- and age-adjusted HRs (95% CIs) of 1.5 (1.2-1.9) and 2.4 (1.8-3.3), respectively. After adjusting for sex, age, the presence of MetS, low serum total cholesterol, chronic kidney disease, anemia, low serum albumin, cognitive impairment, and past history of stroke, the respective multivariable HRs (95% CIs) of loss of independence were 1.5 (1.2-1.9) and 2.1 (1.5-2.9). The magnitude of the risk of loss of independence incidence for frailty was greater among the subjects aged 65-74 years than those aged ≥75 years.Conclusions Frailty was significantly associated with incident loss of independence among elderly Japanese. The presence of MetS had no effect on subsequent onset of disability and mortality in elderly Japanese. Our findings suggest screening and intervention for frailty in the early stage of aging are beneficial to prolong healthy life expectancy of elderly Japanese.