Background Challenges in EUS-guided FNA (EUS-FNA) include sampling error, nondiagnostic cytology, and limited on-site cytological evaluation. A prototype needle-based confocal laser endomicroscopy (nCLE) probe is a submillimeter probe that provides real-time imaging at the microscopic level through the FNA needle. Objective To evaluate the feasibility of nCLE during EUS-FNA of pancreatic lesions. Design Feasibility study. Setting Multicenter, tertiary care. Patients Eighteen patients presenting for EUS-FNA. Interventions Patients were injected with 2.5 mL of 10% fluorescein. The lesion was interrogated with the nCLE probe positioned at the tip of a 19-gauge FNA needle. Main Outcome Measurements Device integrity, technical ease, safety, and image acquisition. Results Cases included 16 cysts and 2 masses. There were no device malfunctions. Technical challenges were encountered in 6 of 18 attempts to image and reflected challenges with a postloading technique, the longer ferule tip, and a transduodenal approach. Technical feasibility to perform imaging with nCLE during a pancreatic EUS-FNA procedure was achieved in 17 of 18 cases. Ten cases had good to very good image quality. Two serious adverse events occurred; both were pancreatitis requiring hospitalization. Limitations Limited sample size, small number of patients with confirmed pathological diagnosis, lack of coregistered pathology and images. Conclusions nCLE in the pancreas is technically feasible via a 19-gauge needle under endosonographic guidance. Future studies will address identification of structures, diagnostic accuracy, and complication profiles. The rate of pancreatitis needs to be further clarified and mitigated.