12 Background: It remains a great challenge to accurately diagnose breast cancer-related lymphedema. Advances in bioelectrical impedance analysis (BIA) permit the assessment of lymphedema by directly measuring lymph fluid changes. Despite its value in assessing lymphedema, the use of BIA in clinical settings is still very limited. In part, this may be due to anecdotal complaints from clinicians about BIA’s ability to identify true case of lymphedema in the clinical settings using L-Dex ratio >+10 as the cutoff point for lymphedema diagnosis. This may also be due to lack of large clinical data to support the reliability, sensitivity, and specificity of using L-Dex ratio. The objective of the study was to examine the reliability, sensitivity, and specificity of BIA in a clinical setting. Methods: BIA was used to measure lymph fluid changes. Data were collected from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema. Reliability, sensitivity, specificity and area under the ROC curve were estimated. Results: BIA ratio, as indicated by L-Dex ratio, was highly reliable among healthy women (ICC=0.99; 95% CI = 0.99 - 0.99), survivors at-risk for lymphedema (ICC=0.99; 95% CI = 0.99 - 0.99), and all women (ICC=0.85; 95% CI = 0.81 – 0.87); reliability was acceptable for survivors with lymphedema (ICC=0.69; 95% CI = 0.54 to 0.80). The L-Dex ratio with a diagnostic cutoff of >+7.1 discriminated between at-risk breast cancer survivors and those with lymphedema with 80% sensitivity and 90% specificity (AUC=0.86). Conclusions: The L-Dex ratio may have a role in clinical practice despite its cost to add confidence in the diagnosis of arm lymphedema among breast cancer survivors. Lymphedema is a progressive and debilitating condition and early treatment usually leads to better clinical outcomes, given that BIA using a diagnostic cutoff of L-Dex ratio > +7.1 still misses 20% of true lymphedema cases, it is important for clinicians to integrate other assessment methods (such as self-report, clinical observation, or perometry) to ensure the accurate diagnosis of lymphedema.