Background: While neoadjuvant chemotherapy is increasingly being using in pancreatic cancer treatment, it is unclear whether it is beneficial in treatment of body and tail tumors. Randomized controlled trials are lacking and previous observational studies have not demonstrated any benefit. We aimed to assess survival associations, trends over time and patient selection associations for multiagent neoadjuvant chemotherapy treated pancreatic cancer of the body and tail using data from the National Cancer Database (NCDB). Methods: We queried the NCDB for pancreatic adenocarcinoma in the body or tail diagnosed between 2010 – 2018 that received multiagent neoadjuvant chemotherapy and/or a distal pancreatectomy. Patients with clinical M1, clinical T4 and surgery other than partial pancreatectomy were excluded. Survival was compared with Kaplan-Meier estimates and multivariable Cox Proportional Hazard Estimates. Results: Between 2010 – 2018, the use of multiagent neoadjuvant chemotherapy increased from 5.7% to 31.8%. In total, 1951 patients were included with n = 384 receiving multiagent neoadjuvant chemotherapy (cases) and n = 1567 undergoing upfront surgery (controls). Neoadjuvant chemotherapy was associated with younger age, tumor in the pancreatic body, clinical N1-2 and with Ca 19-9 ≥98 U/mL. Neoadjuvant chemotherapy was associated with a decreased mortality rate in multivariable Cox regression models adjusting for preoperatively assessed variables (HR 0.65, 95% CI 0.53 – 0.81, p < 0.001) and results were significant in both clinical T1-2 and T3 tumors. Patients treated with upfront surgery had higher rates of adjuvant chemotherapy receipt after resection (41.4% vs 70.6%) but there was no difference in R1 resection rates or 90-day postoperative mortality between the groups. The addition of neoadjuvant radiotherapy was not associated with improved survival in patients receiving neoadjuvant chemotherapy. Conclusions: Multiagent neoadjuvant chemotherapy is increasingly being used in the treatment of pancreatic cancer of the body and tail, especially in younger patients and patients with more aggressive tumor characteristics. Multiagent neoadjuvant chemotherapy is associated with improved survival but randomized trials are needed to establish causal relationships.