Aims: To report surgical outcomes for participants (pts) in the phase 3 KEYNOTE-689 study (NCT03765918) of neoadjuvant and adjuvant pembro + radiotherapy or chemoradiotherapy (RT/CRT) vs surgery and RT/CRT for resectable LA HNSCC. Methodology: Adults with resectable LA HNSCC were randomized 1:1 to neoadjuvant pembro, surgery and adjuvant pembro concurrent with and after RT/CRT vs surgery (pembro group) and RT/CRT only (SOC). Major pathological response (mPR; ≤10% invasive SCC), pathological complete response (pCR), and high-risk pathological features (positive margins [<1 mm] or extranodal extension) were assessed by BIPR and resection outcome by site. Results: 322/363 pts (88.7%) in the pembro group and 308/351 (87.7%) in the SOC group proceeded to surgery. There were 34/363 mPRs (9.4%) and 11/363 pCRs (3.0%) in the pembro group, and no mPRs or pCRs in the SOC group. Resection outcome R0 occurred in 287/322 (89.1%, pembro) and 261/308 pts (84.7%, SOC); R1 in 29 pts (9.0%) and 33 pts (10.7%); R2 in 5 pts (1.6%) and 13 pts (4.2%), respectively. High-risk pathological features were detected in 118 pts (32.5%) and 156 pts (44.4%) in the pembro and SOC groups. 275 pts in each group received any adjuvant therapy; 38.9% and 50.5% in the pembro and SOC groups received concurrent cisplatin. In the SOC group, median (range) time from randomization to surgery was 1.9 wks (0.3–10.4) and from surgery to start of adjuvant therapy was 6.3 wks (3.1–24.7). In the pembro group, median (range) time from end of neoadjuvant therapy to surgery was 3.0 wks (0.3–12.9) and from surgery to start of adjuvant therapy was 6.1 wks (1.7–17.0). Conclusions: A higher number of R0 were observed in the pembro group vs SOC. Neoadjuvant pembro was associated with mPRs/pCRs. Fewer pts in the pembro group had high-risk pathological features and received cisplatin post-surgery. Results support the addition of neoadjuvant and adjuvant pembro to the existing SOC for resectable LA HNSCC.