Transesophageal echocardiograms (TEEs) performed during transcatheter structural cardiac interventions may have higher complications than those performed in the non-operative setting or even those performed during cardiac surgery. However, there are limited data on complications associated with TEE during these procedures. We evaluated the prevalence of major complications among these patients in the United States (US).A retrospective cohort study was conducted using an electronic health record database (TriNetX Research Network) from large academic medical centers across the US for patients undergoing TEE during transcatheter structural interventions from January 2012 to January 2022. Using the American Society of Echocardiography endorsed ICD-10 codes, patients undergoing TEE during a transcatheter structural cardiac intervention, including transaortic, mitral or tricuspid valve repair, left atrial appendage occlusion, atrial septal defect closure, patent foramen ovale closure, and paravalvular leak repair were identified. The primary outcome was major complications within 72 hours of the procedure (composite of bleeding, esophageal and upper respiratory tract injury). The secondary aim was the frequency of major complications, death, or cardiac arrest within 72 hours of patients who completed intraoperative TEE during surgical valve replacement.Among 12,043 adult patients (mean age: 74 years old, 42% females) undergoing TEE for transcatheter structural cardiac interventions, 429 (3.6%) patients had a major complication. Complication frequency was higher in patients on anticoagulation or antiplatelet therapy compared with those not on therapy (3.9% vs. 0.5%, RR: 8.09, p0.001). Compared with those aged65 years, patients aged ≥ 65 years had a higher frequency of major complications (3.9% vs. 2.2%, RR: 1.75, p0.001). Complication frequency was similar among males and females (3.5% vs 3.7%, RR: 0.96, p = 0.67). Among 28,848 patients who completed surgical valve replacement with TEE guidance, 728 (2.5%) suffered a major complication.This study found that more than 3% of patients undergoing TEE during transcatheter structural cardiac interventions have a major complication which is more common among those on anticoagulant or antiplatelet therapy or who were elderly. With a shift of poor surgical candidates to less invasive percutaneous procedures, the future of TEE-guided procedures relies on comprehensive risk discussion and updating practices beyond conventional methods to minimize risk for TEE-related complications.