Background Neoadjuvant therapy is recommended for patients with borderline-resectable pancreatic cancer (BRPC). In this study, we compare survival outcomes of neoadjuvant therapy with upfront surgery. Methods From January 2011 to June 2016, 1415 patients underwent treatments for pancreatic cancer in Samsung Medical Center. Among them, 112 (7.9%) patients were categorized as BRPC by the NCCN 2016 guideline. They were classified by type of initial treatments into neoadjuvant group (NA, N.=26) and upfront surgery group (US, N.=86). Results The median survival duration of all patients was 18.3 months. Patients in the NA group had more T4 disease than those in the US group (38.5% in NA versus 15.1% in the US group; P=0.010). Arterial involvement was more frequent in the NA group (42.3% versus 15.1%; P=0.003). In the NA group, ten (38.5%) patients underwent surgery, and seven of them had complete R0 resection. In the US group, 83 (96.5%) patients received radical surgery, and 42 (48.8%) had R0 resection. In survival analysis according to intent to treat, the overall two-year survival rate was 51.1% in the US group and 36.7% in the NA group (P=0.001). However, among patients who underwent surgery (N.=96), the two-year overall survival rate was not significantly different between the two groups (P=0.089). According to involved vessels, the survival rate was not different between patients with arterial or both arterial and venous involvement and in patients with only venous involvement (P=0.649). Conclusions It is necessary to demonstrate the efficacy of neoadjuvant therapy and to standardize the regimens through large-scale, multicenter, randomized controlled studies.