Stroke associated with atrial fibrillation (AF) is mainly due to embolism of thrombus formed during stasis of blood in the left atrial appendage (LAA). Pathophysiologic correlates of appendage flow velocity as assessed by transesophageal echocardiography (TEE) in patients with AF have not been defined. To evaluate the hypothesis that reduced velocity is associated with spontaneous echocardiographic contrast and thrombus in the LAA and with clinical embolic events, we measured LAA flow velocity by TEE in 721 patients with nonvalvular AF entering the Stroke Prevention in Atrial Fibrillation (SPAF-III) study. Patient features, TEE findings, and subsequent cardioembolic events were correlated with velocity by multivariate analysis. Patients in AF during TEE displayed lower peak antegrade (emptying) flow velocity (Anu(p)) than those with intermittent AF in sinus rhythm during TEE (33 cm/s vs 61 cm/s, respectively, P <.0001). Anu(p) < 20 cm/s was associated with dense spontaneous echocardiographic contrast (P <.001), appendage thrombus (P <.01), and subsequent cardioembolic events (P <.01). Independent predictors of Anu(p) < 20 cm/s included age (P =.009), systolic blood pressure (P <.001), sustained AF (P =.01), ischemic heart disease (P =.01), and left atrial area (P =.04). Multivariate analysis found both Anu(p) <20 cm/s (relative risk 2.6, P =.02) and clinical risk factors (relative risk 3.3, P =.002) independently associated with LAA thrombus. LAA Anu(p) is reduced in AF and associated with spontaneous echocardiographic contrast, appendage thrombus, and cardioembolic stroke. Systolic hypertension and aortic atherosclerosis, independent clinical predictors of stroke in patients with AF, also correlated with LAA Anu(p). Our results support the role of reduced LAA Anu(p) in the generation of stasis, thrombus formation, and embolism in patients with AF, although other mechanisms also contribute to stroke.