Background: Squamous cell carcinomas of the head and neck (SCCHN) account for around 4% of all types of malignant neoplasms. Roughly 50-67% of patients with SCCHN present with locally advanced (LA) disease and 65% of them relapse after primary therapy. The standard of care for LA SCCHN is definitive therapy (DT), a combination of surgery and or radiation therapy (RT), with or without platinum-based chemotherapy/cetuximab (chemo), that has been shown to optimize long term disease control. Advances in surgery/RT have led to improved outcomes, but there have been no FDA approved therapeutic agents for LA SCCHN since cetuximab in 2006. Our objective was to characterize the real-world overall survival (OS) of older adults with LA SCCHN in the US. Methods: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, a linkage of cancer registry and claims data, to identify patients diagnosed with LA SCCHN (first and only cancer) from 2010 to 2017 who initiated a relevant treatment (treatment initiation date defined as index date) and were continuously enrolled in Medicare Parts A, B, and D from 12 months pre-index until death or 12 months post-index. We categorized DT as: no DT, non-surgical DT (concurrent chemo + RT (cCRT) or chemo followed by RT/cCRT), or surgical DT (surgery then RT/cCRT with or without prior chemo) using Medicare claims. Median OS (mOS) estimates and 95% confidence intervals (CI) were estimated using the Kaplan-Meier method starting from index date. Results: We identified 1052 older adults with LA SCCHN (median age 73 years, 37% female, and 81% non-Hispanic white). Overall, median follow up was 26.4 months and primary tumor sites were 52.6% oropharynx, 44.7% oral cavity, and 2.8% hypopharynx. LA patients overall had a mOS of 39.2 months. mOS was lowest in patients with SCCHN of the hypopharynx. Around 58% of patients received a DT regimen and mOS was lower for patients treated with non-DT vs DT regimens (21.8 vs 60.9 months, respectively). mOS differed between DT regimens (Table). Conclusions: In this descriptive analysis, we found that OS differed by site and receipt of DT and that a large proportion (42%) of patients received non-DT regimens. mOS was lower in patients who received non-DT vs DT. Despite available treatment options, there remains a need for novel therapies that can improve outcomes in LA SCCHN. Future analyses should explore differences in OS between subgroups while adjusting for patient demographic and clinical characteristics.