Background: Axillary lymph node dissection (ALND) is the standard of care for patients (pts) with persistent node-positive (N+) disease after neoadjuvant chemotherapy (NAC). In those with a clinical response to NAC, it is appropriate to perform limited axillary surgery to evaluate axillary status, with ALND reserved for those who remain N+. We define the directed-sentinel node biopsy (dSLNB) as pre-operative localization of the previously positive lymph node combined with dual-tracer sentinel node biopsy. We hypothesize that omission of ALND in those that have residual N+ disease after NAC, is associated with less morbidity, without impacting outcomes. Methods: This is a single-institution, retrospective analysis of consecutive pts with N+ breast cancer (BC) who received NAC and dSLNB +/- ALND from 2014-2021. A clip was placed in the positive node at the time of biopsy and excised using radioactive seed localization (RSL) with an I-125 seed. Only those with persistent disease in the RSL on pathology were included (RSL+). We assessed the impact of extent of axillary surgery on primary outcomes, including recurrence, disease-free survival (DFS) and overall survival (OS), and secondary outcomes, including location of recurrence and lymphedema. Results: 156 female pts with N+ BC received NAC, underwent dSLNB +/- ALND with RSL+. Mean age was 52.1 years (SD 12.2). Median follow-up was 32.5 months (IQR 22.9-51.6). Phenotype distribution was 55.8% luminal, 21.2% HER2 positive, and 23.1% triple negative, with no difference between ALND or dSLNB. Pts who had ALND had a higher nodal stage at presentation compared to dSLNB (N1: 72.9% vs. 91.8%, N2: 20.6% vs. 8.2%, N3: 6.5% vs. 0%, p = 0.016). 90.4% received adjuvant radiation with no difference between ALND and dSLNB. Lymphedema rates were higher in the ALND group (47.7% vs. 16.3%, p < 0.001). Fifteen patients died with no difference between ALND and dSLNB in overall mortality rates (9.3% vs. 10.2%, p = 1.000). Nineteen pts recurred with 73.7% occurring at distant sites (ALND 76.5% vs. dSLNB 50%, p = 0.468). There was a higher recurrence rate after ALND (15.9% vs. 4.1%, p = 0.038) as well as higher rates of extracapsular LN extension (46.7% vs. 14.9%, p < .001) and breast lymphovascular invasion (49% vs. 30.4%, p = 0.035). Comparing ALND to dSLNB, there was no difference in DFS (30 months vs. 37 months, p = 0.650) or OS (36.4 months vs. 36.2 months, p = 0.982). Conclusions: For pts with persistent N+ disease in the RSL node after NAC, there was no difference in DFS or OS regardless of extent of axillary surgery. ALND led to higher rates of morbidity, namely lymphedema, but did not contribute to better outcomes. Most recurrences were distant, suggesting aggressive tumor biology as the driver for poor oncologic outcomes rather than the extent of axillary surgery. In this light, the results of the Alliance 11202 are awaited as it answers the question on a randomized, multi-institutional level.