IntroductionThe impact of a positive resection margin (RM+) in appendiceal cancer (AC) remains unclear, with small studies suggesting it does not worsen survival in low-grade subtypes. We aimed to evaluate RM+ rates, its risk factors, and survival outcomes across different AC histologies. MethodsWe conducted a multicenter retrospective cohort study using the National Cancer Database (2004–2019) and including stage I-III AC cases. Surgical and survival outcomes were compared between RM+ and RM- groups, with logistic regression analyzing the association of RM+ and its predictors. Subgroup analysis was performed for low/high tumor grade (LG/HG), mucinous/non-mucinous pathology (MAC/NMAC), and signet ring cell carcinoma (SRC). ResultsAmong 6800 patients identified, 737 (10.8 %) had RM+, while 6063 (89.2 %) had RM-. RM+ rates varied across AC histologies: 10.9 % in LG-MAC, 17.0 % in HG-MAC, 7.8 % in LG-NMAC, 13.9 % in HG-NMAC, and 17.9 % in SRC. RM+ correlated with significantly worse survival in LG-MAC (HR 1.67), HG-MAC (HR 1.83), LG-NMAC (HR 2.04), and SRC (HR 2.37) but not in HG-NMAC after adjusting to other factors. Predictors of RM+ included pT stage, preoperative chemotherapy in LG tumors and pT stage and positive lymph nodes in HG tumors whereas more extensive resection was associated with RM- in both LG and HG. ConclusionRM+ worsens survival in most AC subtypes, highlighting the importance of achieving negative margins. Extensive resection, like right hemicolectomy, can improve RM- rate, but factors such as pT stage, lymph node status, and preoperative chemotherapy also affect RM+. Surgeons should prioritize achieving RM- in all AC histologies.