Background This analysis was performed to assess the impact of early intervention following prospective surveillance using bioimpedance spectroscopy (BIS) to detect and manage breast cancer-related lymphedema (BCRL). Methods From 8/2010 to 12/2016, 206 consecutive patients were evaluated with BIS. The protocol included pre-operative assessment with L-Dex as well as post-operative assessments at regular intervals. Patients with L-Dex scores >10 from baseline were considered to have subclinical BCRL and were treated with over-the-counter (OTC) compression sleeve for 4 weeks. High-risk patients were defined as undergoing axillary lymph node dissection (ALND), receiving regional nodal irradiation (RNI), or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy (CDP). Results Median follow-up was 25.9 months. Overall, 17% of patients had one high-risk feature, 8% two, and 7% had three. 9.8% of patients were diagnosed with subclinical BCRL with highest rates seen following ALND (23 vs. 7%, p  = 0.01). Development of subclinical BCRL was associated with ALND and receipt of RNI. At last follow-up, no patients (0%) developed chronic, clinically detectable, BCRL. Subset analysis was performed of the 30 patients undergoing ALND. Median number of nodes removed was 18 and median number of positive nodes was 2. 77% received taxane chemotherapy, 62% axillary RT, and 48% had elevated BMI. Overall, 86% of patients had at least one additional high-risk feature, 70% at least two, and 23% had all three. Seven patients (23%) had abnormally elevated L-Dex scores at some point during follow-up. To date, none has required CDP. Conclusions The results of this study support prospective surveillance utilizing BIS initiated pre-operatively with subsequent post-operative follow-up measurements for the detection of subclinical BCRL. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with no cases progressing to chronic, clinically detectable BCRL even in very high-risk patients.