Background: LA HNSCC (stage III-IVb) is a potentially curable disease. However, many patients experience recurrence and metastasis, resulting in poorer prognoses. The multimodal approach to treating LA HNSCC makes the evaluation of treatment regimens difficult. This study aimed to describe the real-world treatment patterns, clinical outcomes and HCRU of LA HNSCC patients in England. Methods: This retrospective cohort study involved the use of data from the National Cancer Registration and Analysis Service databases (Cancer Registry, Systemic Anti-Cancer Therapy, Hospital Episode Statistics [HES], National Radiotherapy Dataset and Diagnostic Imaging Dataset). Adults with a first record of primary LA HNSCC between 01/01/2015 and 31/12/2018 were indexed. Treatment pathways and clinical outcomes were investigated over a maximum of 5-years follow-up period extending to 31^st December 2020. Results: 12,790 patients were included within the cohort. 52.1% (n = 6,665) received chemotherapy at some point during follow-up as part of their combination treatment with surgery and/or radiotherapy. Within the chemotherapy receiving cohort, 21.2% (n = 1,413) received induction chemotherapy prior to surgery or radiotherapy, 92.2% (n = 6,145) received concurrent chemo-radiotherapy and 11.8% (n = 787) received chemotherapy following surgery or radiotherapy, suggesting palliative treatment. The majority of chemotherapy regimens used were platinum-based. Of those receiving surgery (n = 5,292), the most common type of surgery was transoral surgery, occurring in 51.3% of the resectable patients. 40.2% of the overall cohort received salvage surgery during follow-up. 50.1% and 12.4% of patients experienced locoregional or distant metastatic progression, respectively and 39.2% of the cohort died. The 5-year overall survival (OS) was ~59% and ~55% for resected and unresected patients respectively. For event free survival (EFS), the 5-year median survival time post event free state index for the overall cohort was 12.32 months. Median survival time for the different tumour sites ranged from 19.4 and 2.6 months, with the nasopharynx and ‘other’ site group representing these range ends respectively. The highest HCRU/costs were incurred within the first 3 months following diagnosis; mean number of HNSCC-related inpatient stays were 2.93 (SD = 4.05), costing a total of £57,781,497 (per patient: £4,855.18 [£5872.05], mean[SD]). Conclusions: This is the first real world study using the UK NCRAS datasets to assess the treatment pathway and outcomes of the LA HNSCC population in England. Survival outcomes varied across site of primary tumour and patients diagnosed at stage 4 experienced poorer outcomes, highlighting the need for improved treatment plans and clinical outcomes for this patient population.