The timing of surgery and antineoplastic therapies in patients with resectable non-metastatic pancreatic cancer is still a controversial matter of debate, with special regard to neoadjuvant approaches. Following the criteria of the PRISMA statement, a literature search was conducted looking for RCTs focusing on adjuvant and neoadjuvant therapies in resectable pancreatic cancer. The quality of the available evidence was assessed using the Cochrane Collaboration's tool for assessing risk of bias. Data extraction was carried out by two independent investigators. The search led to the identification of 2830 papers of which 14 RCTs focusing on adjuvant and neoadjuvant treatment of resectable pancreatic cancer eligible for the systematic review. Risk of bias was estimated "unclear" in 3 studies and "high" in 5 studies. Median age ranged between 53 and 66. Overall survival in the surgery-only arms ranged between 11 and 20.2 months; in the adjuvant treatment arms 12.5-29.8 months; and in the neoadjuvant setting 9.9-19.4 months. Neoadjuvant protocols should be offered only in randomized clinical trials comparing the standard of care (surgery followed by adjuvant treatments) to a neoadjuvant approach followed by surgery and adjuvant treatment.