Objective: To evaluate the impact of clinical and pathological parameters, including resection margin (R) status, on survival in patients undergoing pancreatic surgery after neoadjuvant treatment for initially unresectable pancreatic ductal adenocarcinoma (PDAC). Background: Prognostic factors are well documented for patients with resectable PDAC, but have not been described in detail for patients with initially unresectable PDAC undergoing resection after neoadjuvant therapy. Methods: Prospectively collected data of consecutive patients with initially unresectable pancreatic cancer treated by neoadjuvant treatment and resection were analyzed. The R status was categorized as R0 (tumor-free margin >1 mm), R1 ≤1 mm (tumor-free margin ≤1 mm), and R1 direct (microscopic tumor infiltration at margin). Clinicopathological characteristics and outcomes were compared among these groups and tested for survival prediction. Results: Between January, 2006 and February, 2017, 280 patients with borderline resectable (n = 18), locally advanced (n = 190), or oligometastatic (n = 72) disease underwent tumor resection after neoadjuvant treatment. Median overall survival from the time of surgery was 25.1 months for R0 (n = 82), 15.3 months for R1 ≤1 mm (n = 99), and 16.1 months for R1 direct (n = 99), with 3-year overall survival rates of 35.0%, 20.7%, and 18.5%, respectively (P = 0.0076). The median duration of the neoadjuvant treatment period was 5.1 months. In multivariable analysis, preoperative CA 19–9 levels, lymph node status, metastasis category, and vascular involvement were all significant prognostic factors for overall survival. The R status was not an independent prognostic factor. Conclusions: In patients undergoing resection after neoadjuvant therapy for initially unresectable PDAC, preoperative CA 19–9 levels, lymph node involvement, metastasis category, and vascular involvement, but not the R status, were independent prognostic factors of overall survival.