Background: The incidence of early-onset (age <50) gastrointestinal cancers, including early onset Appendiceal Adenocarcinoma (EOAA) is on the rise, however reported data on etiology, treatment, and outcomes is scarce. Here we present outcomes for EOAA patients treated at a single high-volume center. Methods: Records of patients (pts) with EOAA were reviewed. Clinicopathological and genomic data were abstracted. Pts aged 18 - 49 years at diagnosis with Appendiceal Adenocarcinoma (AA) seen at UCMC between 2013 - 2023 were included. The primary outcome of Overall survival (OS) was analyzed using univariable Cox proportional hazards regression analysis. Results: 116/492 (23.6%) appendix cancer pts seen at UCMC had early-onset disease. 45 pts met eligibility (Table). 10/20 (50%) pts with localized disease had recurrence after hemicolectomy (median recurrence free survival = 41.6 months; 95% CI, 34.3 – NR; follow-up = 46.42 months). 22/44 (50%) pts had mucinous AA, 21 (47.7%) goblet cell AA, and 1 (2.33%) had poorly differentiated AA. In 35 pts with metastatic/recurrent disease, mOS was 35.93 months (95% CI, 28.4 – NR). Lymphovascular (LVI) or perineural invasion (PNI) (HR, 6.41; 95% CI, 2.10 – 19.59, p = 0.001), lymph nodes metastasis (HR, 13.11; 95% CI, 3.53 – 48.68; p < 0.001), and grade 3 disease (vs. grade 1; HR, 5.28; 95% CI, 1.43 – 19.51, p = 0.01) were prognostic for worse OS in univariable analysis. Cytoreductive surgery (CRS), irrespective of completeness, was associated with improved OS (HR = 0.21; 95% CI, 0.09 – 0.53; p < 0.001). Next Generation Sequencing results were available in 20 cases: KRAS (n = 10, 50%), TP53(n = 7, 35%), GNAS (n = 6, 30%), SMAD4 (n = 4, 20%), and MYC (n = 3, 15%) were frequently altered. Alterations with potential therapeutic targets were seen in 12/20 (60%) cases. 10 pts had germline testing with 2 (20%) pathogenic alterations detected: SDHA(H447Mfs*23) and CHEK2 (T367Mfs*15). The pt with CHEK2 mutation had AA as the only malignancy, was the youngest (age 26.17) and passed away 17.26 months after diagnosis. Conclusions: A considerable number of patients with AA may have early-onset disease. A median OS of about 3 years in this young and vulnerable patient population is alarming. As in late-onset disease, EOAA is often incidentally diagnosed. LVI or PNI may be associated with poorer outcomes and deserve additional consideration for risk stratification. Many patients have targetable genomic alterations and should be included in clinical trials where current enrollment is often unsatisfactory for AA. Germline mutation testing in patients with EOAA should be widely implemented.