Abstract Background: Sentinel lymph node biopsy (SLNB) alone is now frequently offered to women with initially node-positive breast cancer who convert to pathologically node negative (nodal pCR) following neoadjuvant chemotherapy (NAC), despite limited long-term data regarding the oncologic safety of this approach. The aim of this meta-analysis was to evaluate the long-term oncologic outcomes associated with SLNB alone following NAC for initially node-positive breast cancer. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Medline (Ovid), Embase, and Cochrane Central Registry were systematically searched for studies comparing women undergoing SLNB or ALND following NAC for initially clinically node-positive breast cancer. Included studies reported one of the following outcomes: axillary recurrence (AR), locoregional recurrence (LRR), disease-free survival (DFS) or overall survival. A random effects meta-analysis was used to calculate weighted pooled effect estimates (risk ratios, RR) for all outcomes. Variability across studies due to heterogeneity was estimated using I2 statistics. Subgroup analysis was performed by length of follow-up for each study. Risk of bias within studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: Data for participants undergoing treatment between 2004 and 2022 was captured across studies. The median age of women treated with NAC for initially node-positive breast cancer ranged from 46 to 60 years. The median follow-up time ranged from 19.5 to 108 months across included studies. Nine observational studies were eligible for meta-analysis. No studies were excluded from the analysis on the basis of quality: Newcastle-Ottawa Scale scores ranged from 6 to 9 (maximum possible score of 9). Rates of axillary recurrence (AR) were low across all included studies (range 0.0% to 5.6%). For AR, data for 2,882 patients from 7 studies was quantitatively synthesized (SLNB=1,964; ALND=917). For LRR, data for 2,629 patients from 7 studies was quantitatively synthesized (SLNB=1,857; ALND=771). No significant differences were observed in AR between patients undergoing SLNB alone versus ALND following NAC for initially node-positive breast cancer: pooled RR 1.02 (95% CI: 0.46-2.29, I2=0.0%). Similarly, no significant differences were observed in LRR (RR 0.70, 95% CI: 0.45-1.10, I2=0.0%), DFS (RR 0.77, 95% CI: 0.55-1.08, I2=0.0%), nor overall mortality (RR 0.66, 95% CI: 0.33-1.33, I2=0.0%) between the SLNB and ALND groups. Conclusions: Among patients who convert to node-negative following NAC, this meta-analysis suggests that SLNB alone does not result in significantly different oncologic outcomes compared to ALND, and that de-escalation of axillary surgery to SLNB alone in this context may be safely considered in this patient population. Citation Format: Mariam Rana, Anna Weiss, Alison Laws, Carol Mita, Tari King. Long-term outcomes of sentinel lymph node biopsy following neoadjuvant chemotherapy for initially node-positive breast cancer: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-02.