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BACKGROUND: This is a prospective, single-institution study to evaluate feasibility and accuracy of radar-localized reflector (RLR)–targeted axillary dissection (TAD) in node-positive breast cancer patients after neoadjuvant systemic therapy (NST). METHODS: Patients with biopsy-proven T1–2, N1–3 disease were eligible. Before NST, a marker clip and/or RLR was placed into the positive node. After NST, RLR was inserted if not placed previously. All patients underwent RLR TAD followed by axillary lymph node dissection (ALND). Primary end points of the trial were feasibility of RLR TAD and false negative rate (FNR). RESULTS: Between 2017 and 2021, 101 patients with N1–3 disease underwent NST. Five patients withdrew from the study, 1 was ineligible, and there were 9 technical failures, thus our final study cohort comprised 86 patients. RLR TAD was performed with probe guidance and confirmed with intraoperative specimen radiograph. After RLR TAD, ALND was performed. Median number of RLR TAD nodes removed was 2 (range 1–10), and the RLR TAD nodes remained positive in 56 patients. Median number of ALND nodes removed was 18 (range 4-46). Accounting for 9 technical failures, feasibility was 90%. All technical failures occurred with attempted placement of RLR after NST. Feasibility rate was 100% when RLR placement occurred at diagnosis. Of the evaluable 86 patients, RLR TAD accurately predicted axillary status in 83 patients, with FNR of 5.1%. CONCLUSION: We demonstrate high accuracy of RLR TAD, especially when RLR is placed before NST. For patients who present with N1–3 disease, this is another step towards axillary surgery de-escalation strategies.