Background <p>Low and high body mass index (BMI) are reported to be associated with frailty in older adults. Since the optimal BMI associated with a low risk of mortality varies with age, the association between BMI and frailty might also differ by age. This study examined the association between BMI and frailty in middle-aged and older adults in Japan.</p> Methods <p>We conducted face-to-face and mail surveys in Settsu city and mail survey in Hannan city in Osaka, Japan. The association between BMI and frailty was analyzed among 8,815 participants using mail surveys. Frailty was evaluated using two tools, the Kihon Checklist (KCL) and the Frailty Screening Index (FSI). BMI (kg/m²) was categorized into the &lt; 18.5, ≥ 18.5–&lt;20.0, ≥ 20–&lt;22.5, ≥ 22.5–&lt;25.0, ≥ 25.0–&lt;27.5, and ≥ 27.5&#xa0;kg/m² groups. We analyzed the association between BMI and frailty using multivariable logistic regression, with BMI ≥ 22.5–&lt;25.0&#xa0;kg/m² as the reference to calculate the odds ratios (OR) and 95% confidence intervals (95%CI). Restricted cubic spline analyses were also performed, with knots placed at the 5th, 50th (as reference), and 95th percentiles of BMI. We performed all analyses separately for the &lt; 65 and ≥ 65 years age groups.</p> Results <p>BMI &lt; 18.5 (OR = 1.882, 95%CI: 1.263–2.805) was significantly associated with KCL-measured frailty in individuals aged &lt; 65 years, and BMI &lt; 18.5 (OR = 1.807, 95%CI: 1.291–2.531) and ≥ 27.5 (OR = 1.562, 95%CI: 1.156–2.111) were significantly associated with KCL-measured frailty in those aged ≥ 65 years. BMI ≥ 25.0–&lt;27.5 (OR = 1.426, 95%CI: 1.055–1.927) and ≥ 27.5 (OR = 1.473, 95%CI: 1.093–1.985) were significantly associated with FSI-measured frailty in individuals aged &lt; 65 years, and BMI ≥ 27.5 (OR = 1.988, 95%CI: 1.432–2.759) was significantly associated with frailty in those aged ≥ 65 years. The spline models showed U-shaped associations for KCL-measured frailty for both age groups, a positive linear association for FSI-measured frailty among those aged &lt; 65 years, and an L-shaped association for FSI-measured frailty among those aged ≥ 65 years.</p> Conclusion <p>The association between BMI and frailty differed by age. The collation of all the results of this study suggests that both low and high BMI are associated with frailty in middle-aged and older adults. Based on the results, it is speculated lifestyle habits that promote proximity to “normal weight” may help prevent frailty.</p> Trial registration <p>UMIN000008105 (Registration date: May 29th 2019; Website: <a href="https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042027">https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042027</a>).</p>