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Introduction: Little knowledge exists on the pathogenesis and the recovery of dysphagia in supratentorial stroke. This longitudinal lesion study aims to define critical nodes of the supratentorial neuronal network underlying swallowing and to establish MRI based predictors of impaired recovery from dysphagia in ischemic stroke patients. Methods: A review of the literature yielded 11 supratentorial regions of interest (ROI) related to swallowing in healthy individuals. Atlas-based localization analysis of these ROIs was performed using Talairach alignment of brain scans in consecutive patients with MRI-proven first-time acute supratentorial stroke. Standardized swallowing assessment was carried out within 48 hours and 8 to 10 days after admission. Results: In a prospective analysis of 94 patients, 34 (36%) were classified as having acute dysphagia, which was prolonged (>7 days) or transient (<=7 days) in 17 (18%) cases respectively. There were no between group differences in age, gender, stroke etiology, risk factors, pre-stroke disability, lesion side or the degree of age related white matter changes. In patients with acute dysphagia, the NIH Stroke Scale (7,5 +- 11 vs. 4 +- 6, p=0.008) and the lesion size (21ml +- 59 vs. 6ml +- 17, p=0.002) were shown to be the two most significant location-independent predictors. Correcting for these two confounders with a multiple logistic regression model, significant adjusted odds ratios (aOR) of acute dysphagia were demonstrated for the internal capsule (aOR=5.3, p=0.003), the insular cortex (aOR=3.7, p=0.012) and the periventricular white matter (aOR=3.5, p=0.012). In a multivariate model of prolonged vs. transient dysphagia significant odds were demonstrated only for the frontal operculum (aOR=37.4, p=0.007). Conclusions: The insular cortex, the internal capsule and the periventricular white matter (PVWM) represent critical relay nodes of the supratentorial neuronal network underlying swallowing. Lesions of these regions are associated with significantly elevated odds of acute dysphagia. Lesions of the frontal operculum substantially influence the recovery of swallowing function in dysphagic stroke patients, whereas dysphagia tends to be transient in subcortical stroke.