For a study, researchers sought to understand that the gold standard of care is salvage surgery, although only a small percentage of patients experience long-term improvement. Some individuals have adjuvant radiation, also referred to as chemo-radiotherapy, even though it can be extremely risky. They looked into the efficacy and safety of adjuvant nivolumab in light of the activity and toleration of programmed death-1 inhibitors in metastatic HNSCC. An open-label, multi-institutional phase II clinical study was conducted here (NCT03355560). About 6 weeks following salvage surgery, patients with HNSCC that recurs but is treatable were included. Adjuvant nivolumab regimens of six 28-day cycles were planned. Based on a historical institutional control group of 71 patients with recurrent HNSCC who underwent salvage surgery, the primary goal was 2-year disease-free survival (DFS) better than 58%. About 39 persons were involved between February 2018 and February 2020. The 2-year DFS was 71.4% [95% CI, 57.8-88.1], and the 2-year overall survival (OS) was 73% [95% CI, 58-91.8] after a median follow-up of 22.1 months. About 39 individuals (8%) who had treatment-related grade 3 adverse events stopped it because of side effects. About 10 of the 39 patients had locoregional recurrence, and 2 had synchronous metastatic disease. Between PD ligand-1 (PD-L1) positive and PD-L1 negative patients, there was no difference in DFS. Patients with a high tumor mutational burden showed a nonsignificant tendency toward better DFS (P=0.083). Adjuvant nivolumab exhibited increased DFS compared to historical controls and was well tolerated in locally recurrent HNSCC after salvage surgery.