Background: Internal jugular cannula position is traditionally confirmed via plain film at the conclusion of the peripheral ECMO cannulation procedure. However, it may be difficult to estimate the location of the right atrium on plain films. A misplaced cannula can result in need for repositioning and increased morbidity. Echocardiography (ECHO) may be used during cannulation as a more accurate means of guiding cannula position. The aim of this study is to study the effect of a protocol encouraging the routine use of ECHO at the time of cannulation. Objective: To assess whether the use of echocardiographic guidance during neonatal and pediatric jugular cannulation for ECMO reduces the need for cannula repositioning or decreases morbidity. Methods and Materials: We performed a retrospective review of patients at a single institution who received ECMO support using jugular venous cannulation from January 2013 through October 2016. We compared those who underwent ECHO (ECHO+) at the time of cannulation with those who did not (ECHO-). Patient demographics and surgical history, ECMO cannulation details, ECMO events, need for cannula repositioning, cannula related morbidity, and patient outcomes were noted. The results were analyzed with descriptive and non-parametric statistics where applicable. Results: 89 patients met inclusion criteria: 26 ECHO+ (29%), 63 ECHO-(71%). Most of ECHO+ patients underwent dual-lumen VV cannulation (n=17, 65%), while 32% of ECHO-patients had VV support (p<0.003). Seven (27%) ECHO+ patients and 18 (28%) ECHO-patients had a history of cardiac surgery prior to ECMO (p=0.88). All patients had CXR to verify cannula position, and fluoroscopy was used in 4 ECHO+ patients but no ECHO-patients. There was a major mechanical complication in each group: atrial perforation from a guidewire during cannulation in ECHO+ and late atrial perforation from a loose cannula in ECHO-. Subsequent to cannulation, there were 0.58 ECHO studies per patient to verify cannula position in the ECHO+ group compared to 0.22 ECHO per patient in the ECHO-group (p=0.02). Two (8%) ECHO+ patients required a cannula repositioning procedure for misplacement during the ECMO run, while 6 (10%) ECHO-patients required repositioning procedures (p=0.78). In the VV ECMO subgroup, ECHO+ patients required no repositioning, while 4 (20%) of ECHO-VV patients required repositioning (p=0.1). Patients who had ECHO to verify cannula placement during the ECMO run were more likely to have a repositioning procedure (p<0.001). Repositioning procedures resulted in no additional complications. Survival to discharge was similar in both groups: 54% ECHO+ and 62% ECHO-(p=0.51).