Background: Histological grade is a key prognostic factor in appendiceal adenocarcinomas (AAs) and has been incorporated in classification of stage IV AAs (IVA – Grade 1: Well; IVB – Grade 2/3: Moderately/Poorly differentiated) in AJCC Cancer Staging (8th edition). The purpose of the study was to corroborate the prognostic impact of this staging classifier. Methods: We performed a retrospective review of 98 AA patients (pts) at UTMDACC (2013 - 2017). Kaplan-Meier method was used to estimate median overall survival (mOS), compared with log-rank tests with emphasis on stage and grade. Results: The cohort included 18, 8, 14, 47 and 11 cases of stage II, III, IVA, IVB and IVC AAs. Histologically, 75 were mucinous (21 non mucinous) and 19, 35 and 42 were grade 1, 2 and 3 respectively. Median age of cohort was 54 years. Median follow-up was 46 months (m). The mOS of stage II, III, IVA, IVB and IVC was 136, 106, 140, 48, 23 m, respectively (P < 0.0001). The mOS of grade 1, 2 and 3 was 160, 75 and 33 m, respectively (P < 0.0001). In univariate analysis (restricted to stage IV pts), grade, AJCC stage, and cytoreductive surgery (CRS) were found to be associated with OS. In multivariate analyses (restricted to stage IV pts), only AJCC stage (HR 3.9, 95% CI: 1.5 - 10.6, P = 0.005) and CRS (HR 3.4, 95% CI: 1.4 – 8.3, P = 0.009) were found to be independently associated with poor OS. In subgroup of mucinous AAs, mOS of grade 3 (32 m) was significantly shorter than grade 2 (54 m) (P = 0.02). In non-mucinous AAs, mOS of grade 3 and grade 2 pts was 38 and 29 m, respectively (P = 0.97). Conclusions: AJCC staging classification has a strong prognostic value in AAs. Beyond the well differentiated AAs which are regarded as a distinct entity in stage IV disease, moderate and poor differentiation also has strong and dissimilar prognostic impact which appears to be dependent on mucinous or non-mucinous subtype in stage IV AAs. Further efforts are needed to incorporate the complex interplay of all grades and mucinous characteristics within the staging system for better prognostication and management.