A trial-level meta-analysis was conducted to determine the relative risk (RR) of pancreatitis associated with multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without an FDA-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, axitinib, vandetanib, cabozantinib, ponatinib, regorafenib). Statistical analyses calculated the RR and 95% confidence intervals (CI). A total of 10,578 patients from 16 phase III trials and 6 phase II trials were selected. The RR for all grade and high-grade pancreatitis for the TKI vs. no TKI- arms was 1.95 (p = 0.042, 95% CI: 1.02 to 3.70) and 1.89 (p=. 0.069, 95% CI: 0.95 to 373), respectively. No differential impact of malignancy type or specific TKI agent was seen on RR of all grade of high grade pancreatitis. Better patient selection and monitoring may mitigate the risk of severe pancreatitis.