Background: This study aimed at testing whether arm-to-leg ratios of extracellular water (ECW) and ECW normalized to intracellular water (ICW), measured by bioimpedance spectroscopy (BIS), can accurately detect bilateral, lower-limb lymphedema, and whether accounting for sex, age, and body mass index (BMI) improves the diagnostic performance of cut-offs. Methods and Results: We conducted a dual-approach, case-control study consisting of cases of bilateral, lower-limb lymphedema and healthy controls who self-reported absence of lymphedema. The diagnostic performance using normative data-derived cut-offs (i.e., mean + 0.5 standard deviation [SD] to mean + 3 SD; n = 136, 66% controls) and receiver operating characteristic (ROC) curve-derived cut-offs (n = 746, 94% controls) was assessed. The impact of sex, age, and BMI was investigated by comparing stratified and nonstratified normative data-derived cut-offs, and ROC curves generated from adjusted and unadjusted logistic regression models. Arm-to-leg ratios of ECW between mean + 0.5 SD and mean + 1 SD showed fair to good sensitivity (0.73-0.84) and poor to good specificity (0.64 to 0.84). Arm-to-leg ratios of ECW/ICW failed to detect lymphedema (sensitivity <0.5). Stratification by sex, or by sex and age, yielded similar results to nonstratified cut-offs. Cut-offs derived from adjusted ROC curves showed both good sensitivity (0.83-0.89) and specificity (0.8-0.84). Conclusion: These findings represent new BIS criteria for diagnosing lower-limb lymphedema that do not rely on comparison to baseline measures or the presence of a nonaffected, contralateral limb.