Abstract Background Endoscopic resection (ER) is curative for Barrett’s oesophagus-related early-stage oesophageal adenocarcinoma (EAC) without high-risk features, such as lymphovascular invasion (LVI), positive margins (R1), and deep submucosal invasion (T1bsm2-3). Piecemeal endoscopic mucosal resection (pEMR), often used for lesions larger than 15mm, prevents assessment of lateral margins and therefore complicates precise risk estimation for residual EAC at the first post-ER endoscopy. Thus, we investigated alternative clinical factors that could potentially be used to assess the risk for residual and recurrent EAC post-ER. Methods We performed a longitudinal cohort study of patients who underwent ER between 2006-2023. Inclusion criteria were: T1a or well/moderately differentiated T1bsm1 EAC; LVI-, and R0 resection. ER was categorised as pEMR (n=106) or en-bloc ER (n=22 en-bloc EMR, n=9 endoscopic submucosal dissection). The primary outcome was residual EAC at first post-ER endoscopy. Secondary outcomes were residual HGD at first post-ER endoscopy, EAC and HGD recurrence at any post-ER endoscopy, and remission of EAC, HGD and intestinal metaplasia (IM) at latest endoscopy. Multivariate logistic regression, receiver operating characteristics, chi-squared, and Kaplan Meier analyses were performed to investigate possible associated risk factors. Results Rates of EAC/HGD recurrence were higher post-pEMR versus en-bloc ER (p=0.019), with residual EAC at first post-ER endoscopy accounting for 34% of post-pEMR recurrence. The percentage of pEMR specimens with EAC (p=0.022) and T1bsm1 staging (p=0.013) were independent risk factors for residual EAC at first post-pEMR endoscopy (Table 1). A 53.5% cut-off of involved pEMR specimens was identified as the optimal threshold for residual EAC prediction (specificity=0.68, sensitivity=0.67). Indeed, residual (p=0.012) and recurrent (p=0.00077) EAC rates were higher when EAC involvement was >53.5%. However, rates of EAC (p=0.13), HGD (p=0.19) and IM (p=0.76) remission were unaffected by high EAC burden. Conclusions High burden of EAC on pEMR specimens correlates with increased risk of residual and recurrent EAC at post-pEMR endoscopy. Post-pEMR site check is recommended prior to endoscopic ablation, particularly in patients where more than 50% of pEMR specimens show EAC and in cases of flat subtle lesions. This will ensure eradication of any residual disease and high success rates for treatment of early EAC using endotherapy.