Background EUS-guided FNA (EUS-FNA) permits both morphologic and cytologic analysis of lesions within or adjacent to the GI tract. Although previous studies have evaluated the accuracy of EUS-FNA, little is known about the complications of EUS-FNA. Moreover, the frequency and severity of complications may vary from center to center and may be related to differences in individual experience. Objective To systematically review the morbidity and mortality associated with EUS-FNA. Design MEDLINE and EMBASE were searched to identify relevant English-language articles. Main Outcome Measurements EUS-FNA-specific morbidity and mortality rates. Results We identified 51 articles with a total of 10,941 patients who met our inclusion and exclusion criteria; the overall rate of EUS-FNA-specific morbidity was 0.98% (107/10,941). In the small proportion of patients with complications of any kind, the rates of pancreatitis (36/8246; 0.44%) and postprocedure pain (37/10,941; 0.34%) were 33.64% (36/107) and 34.58% (37/107), respectively. The mortality rate attributable to EUS-FNA-specific morbidity was 0.02% (2/10,941). Subgroup analysis showed that the morbidity rate was 2.44% in prospective studies compared with 0.35% in retrospective studies for pancreatic mass lesions ( P = .000), whereas it was 2.33% versus 5.07% for pancreatic cysts ( P = .036). Limitations Few articles reported well-designed, prospective studies and few focused on overall complications after EUS-FNA. Conclusions EUS-FNA-related morbidity and mortality rates are relatively low, and most associated events are mild to moderate in severity.