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Transcatheter aortic valve replacement (TAVR) is increasingly being performed in cardiac catheterization laboratories using transthoracic echocardiography (TTE) to guide valve deployment. The risk of paravalvular regurgitation (PVR) remains a concern.We retrospectively reviewed 454 consecutive patients (mean age, 82 ± 8; 58% male) who underwent transfemoral TAVR at Emory Healthcare from 2007 to 2014. Two hundred thirty-four patients underwent TAVR in the cardiac catheterization laboratory with TTE guidance (TTE-TAVR; mean Society of Thoracic Surgeons score, 10%), while 220 patients underwent the procedure in the hybrid operating room with transesophageal echocardiography (TEE) guidance (TEE-TAVR; mean Society of Thoracic Surgeons score, 11%). All patients received an Edwards valve (SAPIEN 55%, SAPIEN-XT 45%). Clinical and procedural characteristics, echocardiographic parameters, and incidence of PVR were compared.The incidence of at least mild PVR at discharge was comparable between TTE-TAVR and TEE-TAVR (33% vs 38%, respectively; P = .326) and did not differ when stratified by valve type. However, in the TTE-TAVR group, there was a higher incidence of second valve implantation (7% vs 2%; P = .026) and postdilation (38% vs 17%; P < .001) during the procedure. Although not independently associated with PVR at discharge (odds ratio = 1.12; 95% CI, 0.69–1.79), TTE-TAVR was associated with PVR-related events: the combined outcome of mild PVR at discharge, intraprocedural postdilation, and second valve insertion (odds ratio = 1.58; 95% CI, 1.01–2.46). There were no significant differences in PVR at 30 days, 6 months, and 1 year between the two groups.TTE-TAVR in a high-risk group of patients was associated with increased incidence of intraprocedure PVR-related events, although it was not associated with higher rates of PVR at follow-up. Multicenter randomized trials are required to confirm the cost-effectiveness and safety of TTE-TAVR.Minimalist transthoracic echocardiography (TTE)–guided transcatheter aortic valve replacement (TAVR) is increasingly performed in cardiac catheterization laboratories.Patients undergoing TTE-TAVR were more likely to receive balloon postdilation and second valve placement.Paravalvular regurgitation at discharge was not increased with TTE-guided TAVR.