Abstract Background: The KEYNOTE-522 trial demonstrated that the addition of neoadjuvant pembrolizumab to neoadjuvant chemotherapy (NAC) for the treatment of early-stage triple negative breast cancer (TNBC) significantly improves rates of both pathologic complete response (pCR) and event-free survival. The impact of adding immunotherapy to NAC on surgical outcomes, however, is unknown. The purpose of this study is to compare 90-day surgical complication rates and timing to subsequent adjuvant therapy of patients undergoing neoadjuvant chemotherapy for stage I-III TNBC with and without immunotherapy. Methods: Patients treated at University of California, Los Angeles with neoadjuvant therapy for TNBC between 2018-2022 were identified retrospectively. Patient comorbidities, tumor characteristics, type of surgery, 90-day postoperative minor and major complications, timing to adjuvant therapy, and oncologic outcomes were reviewed and analyzed. Major complications were defined as those requiring reoperation or hospitalization. Results: A total of 44 patients were included, 15 patients received neoadjuvant chemotherapy with immunotherapy (NAC-I) and 29 patients received neoadjuvant chemotherapy alone (NAC). There was no difference in patient comorbidities between the groups. Compared to the NAC group, significantly more patients in the NAC-I group had stage II or III tumors (58.6% vs. 86.7%, respectively, p=0.028). 73% of patients in the NAC-I group underwent mastectomy compared to only 44% of patients in the NAC group (p=0.111). In total, 23 patients underwent reconstruction with mastectomy, 6 patients underwent immediate DIEP flap (4 in NAC-I group and 2 in NAC group) and 17 underwent immediate tissue expander (7 in NAC-I and 10 in NAC group). 80% of patients in the NAC-I experienced a pCR compared to only 44% in the NAC group (p=0.026). A total of 15 patients (34.1%) experienced surgical complications and there was no significant difference in the complication rate between the groups (p= 0.552). Five patients (33%) in the NAC-I group experienced minor complications of seroma requiring aspiration (n=4), cellulitis requiring antibiotics (n=1), or wound dehiscence requiring local wound care (n=2). No patients in the NAC-I group had major complications. Ten patients (33%) in the NAC group experienced complications, including 6 minor complications and 4 major complications including postoperative bleeding or flap necrosis requiring unplanned return to surgery or hyperbaric oxygen treatment. On multivariable regression analysis, controlling for patient characteristics, tumor stage, and preoperative immunotherapy, only younger age was a statistically significant variable associated with increased risk of surgical complications (p=0.012). Median time to adjuvant therapy, including radiation and/or systemic therapy, was similar between NAC-I and NAC groups, at 32 and 36 days, respectively (p=0.37). In the NAC-I group, 14 patients (93.3%) had adjuvant systemic therapy including pembrolizumab alone (n=12), pembrolizumab with olaparib (n=1) or capecitabine alone (n=1). In the NAC group, 11 patients (37.9%) underwent adjuvant systemic treatment including chemotherapy with either capecitabine (n=1), pembrolizumab (n=1), or olaparib (n=2); or single agent capecitabine (n=6) or olaparib (n=1). Conclusions: Despite patients in the NAC-I group having more advanced stage tumors and undergoing more extensive surgery and reconstruction compared to those in the NAC alone group, a significantly higher rate of surgical complications was not observed in the NAC-I group and there was no significant difference in time to adjuvant therapy between the two groups. Similar to results from the KEYNOTE-522 trial, more patients in the NAC-I group experienced a pCR compared to NAC alone. Larger studies are needed to continue to assess and optimize the surgical safety of neoadjuvant immunotherapy with chemotherapy in patients with TNBC. Citation Format: Anouchka Coste Holt, Maurice Berkowitz, Nicholas McAndrew, Courtney Smith, Jennifer Baker, Nimmi Kapoor. Surgical outcomes after neoadjuvant chemotherapy with and without immunotherapy in patients with triple negative breast cancer [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 PO2-22-10.