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The optimal surgical approach and extent of lymph node dissection for esophagogastric junction (EGJ) cancer remains uncertain. We conduct a nationwide multicenter prospective study in patients with resectable cT2-T4 adenocarcinoma or squamous cell carcinoma with the tumor epicenter located within 2 cm of the EGJ. Patients undergo subtotal or lower esophagectomy with dissection of all regional lymph nodes. Of 1,065 patients screened, 371 are enrolled before surgery. Final analysis shows that proximal perigastric and suprapancreatic nodes exhibit a high therapeutic efficacy index (TEI), strongly supporting their dissection for improved long-term survival. TEIs in middle and lower para-esophageal stations are higher when esophageal involvement exceeds 3 and 2 cm, respectively. Conversely, all other stations, including distal perigastric and paraaortic nodes, have low TEIs, indicating minimal survival impact. Thus, mediastinal node dissection should be tailored to esophageal involvement length. This study is registered at UMIN Clinical Trials Registry (UMIN000013205).