Negative-margin resection is crucial to favorable prognosis in patients with pancreatic ductal adenocarcinoma. However, the definition of a negative superior mesenteric artery margin (SMAM) varies. The College of American Pathologists defines positive SMAM as the presence of tumor cells at the margin, whereas the European protocol is based on a 1 mm clearance. In this study, we examined the prognostic significance of the SMAM distance in 411 consecutive pancreatic ductal adenocarcinoma patients who completed neoadjuvant therapy and pancreaticoduodenectomy. Per College of American Pathologists criteria, 32 (7.8%) had positive margins, and 379 (92.2%) had negative margins. Among margin-negative group, SMAM was ≤ 1, 1.0 to 5.0, and >5.0 mm in 66, 145, and 168 patients, respectively. There was no difference in either disease-free survival (DFS) or overall survival (OS) between the positive-margin group and SMAM ≤ 1 mm (P > 0.05). However, patients with SMAM 1.0 to 5.0 mm had better OS than those with positive margins or SMAM ≤ 1 mm (P = 0.02). Patients with SMAM > 5.0 mm had better DFS and OS than those with SMAM 1.0 to 5.0 mm and those with positive margins or SMAM ≤ 1 mm (P < 0.01). By multivariate analysis, the SMAM distance, tumor differentiation, lymph node metastasis, and histopathologic tumor response grade were independent prognostic factors for both DFS and OS. SMAM distance correlated with lower ypT and AJCC stages, smaller tumor size, better histopathologic tumor response grade, fewer lymph node metastases, and recurrences (P < 0.05). Thus our results strongly support use of SMAM > 1 mm for R0 resection in posttherapy pancreaticoduodenectomy specimens.