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Background and Purpose — Severe motor deficits are the predominant cause of long-term disability in stroke patients. In particular, progressive hemiparesis in the initial stage after stroke onset is frequently devastating. Therefore, we attempted to define the population at risk with respect to the presumed pathogenesis. Methods — Among 941 stroke patients hospitalized during a 3-year period, 92 patients (41 men, 51 women; mean age, 68 years) had a severe motor deficit (<25 of 42 points on the 7 motor items of the European Stroke Scale) resulting from brain infarcts. Risk factors, neurological examinations, comprehensive diagnostic tests, and therapy were documented. The study population was separated into patients with (group A) and without (group B) progressive motor deficits. Progression was defined as a further decrease of at least 5 points on the initial European Stroke Scale motor score during the first 5 days after stroke onset. Results — Of the 92 patients, 23.9% had significant worsening of motor function with a decrease in the mean European Stroke Scale motor score from 20.3 to 12.9 points ( P <0.01). Infarcts in group A patients were subcortical in 59.1%, whereas most infarcts were cortical in group B (61.4%, P <0.05). Progressive hemiparesis was also significantly associated with lacunar stroke (group A:, 59.1%; group B, 24.3%; P <0.01). With regard to risk factors, diagnostic studies, and neuroimaging, small-vessel disease was the predominant presumed cause of stroke in group A (63.6%, P <0.01), whereas infarcts in group B patients were frequently caused by embolism from cardiac or undetermined sources (61.4%, P <0.01). Prevalence of high-grade carotid stenosis was not significantly different between groups A and B; however, subtotal stenoses and complete internal carotid artery occlusions were found only among patients without progressive motor deficits. Conclusions — Lacunar stroke caused by small-vessel disease is the major cause of progressive motor deficits, probably because of stepwise occlusion of the branches of small penetrating arteries.