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Intraoperative consultation (IOC) on surgical margins during curative intent resection of gastric and gastroesophageal adenocarcinoma presents sampling and interpretive challenges. A false-negative (FN) IOC result can affect clinical care. Many factors may be associated with higher risk for an FN result of IOC on surgical margins.To assess the prevalence and clinical implications of FN results of IOC on surgical margins during resection of gastric and gastroesophageal adenocarcinoma.This retrospective study assessed the results of IOC on surgical margins to determine the prevalence of FN results and the accuracy and clinical implications of the results for patients undergoing curative intent resection for gastric or gastroesophageal adenocarcinoma. The study examined patients with gastric or gastroesophageal adenocarcinoma who underwent resection with curative intent at a single-institution referral center from January 1, 1992, to December 31, 2015.Curative intent gastric and/or esophageal resection.False-negative results of IOC on surgical margins, accuracy of the results, factors associated with decreased accuracy of the results, and clinical implications of FN results.This study included 2002 patients (median age, 65 years; 1343 [67.1%] male; 1638 [81.8%] white) who received 3171 IOCs on surgical margins. Of the 3171 IOCs, the prevalence of FN results was 1.7%, with an accuracy of 98.1%. The prevalence of an FN IOC result was 1.2% for esophageal margins, 2.0% for gastric margins, and 2.5% for duodenal margins (P = .04). The prevalence of an FN IOC result was higher for patients with diffuse or signet ring disease compared with those without (2.6% vs 1.2%, P = .002) and for those not receiving neoadjuvant radiotherapy compared with those receiving neoadjuvant radiotherapy (1.4% vs 0.7%, P < .001). The prevalence of FN results of IOCs performed by nongastrointestinal pathologists was similar to that of IOCs performed by gastrointestinal pathologists (2.3% vs 1.9%, P = .60). The disease-specific survival was 34 months (95% CI, 20.7-47.2 months) for those with an FN result and 26.9 months (95% CI, 18.3-35.4; P = .72) for those with a true-positive result. Half of the patients with FN IOC results received further margin-directed therapy, including subsequent resection or radiotherapy.This study found that IOC on surgical margins was accurate at a specialty center. Signet ring or diffuse disease, duodenal margins, and not receiving neoadjuvant radiotherapy were challenging scenarios for IOC on surgical margins. The use of IOC on surgical margins may be optimal when it will affect intraoperative decision making framed by the stage of disease, tumor location, and surgical fitness of the patient.