Background and Purpose The quality of after-hour emergency care of patients with acute ischemic stroke is debatable. We therefore, sought to analyze the performance measures, quality of care and clinical outcomes in these patients admitted during off-hours. Methods Our study included 4493 patients from a selected cohort of patients admitted to the hospitals with ischemic stroke in the China National Stroke Registry (CNSR) from September 2007 to August 2008. On-hour presentation was defined as arrival at the emergency department from the scene between 8AM and 5PM from Monday through Friday. Off-hours included the remainder of the on-hours and statutory holidays. The association between off-hour presentation and outcome was analyzed using multivariate logistic-regression models. Results Off-hour presentation was identified in 2672 (59.5%) patients with ischemic stroke. Comparison of patients admitted during off-hours with those admitted during on-hours revealed an unadjusted odds ratio of in-hospital mortality of 1.38 (95% confidence interval, 1.04-1.85), which declined to 1.34 (95% confidence interval, 0.93-1.93) after adjusting for patient characteristics (especially, pre-hospital delay). No difference in 30-day mortality, total death or dependence at three, six and 12 months between two groups was observed. No association between off-hour admission and quality of care was found. Conclusions In the CNSR database, compared with on-hour patients, off-hour patients with acute ischemic stroke admitted to the emergency departments from scene manifested a higher incidence of in-hospital mortality. However, the difference in incidence and quality of care between the groups disappeared after adjusting for pre-hospital delay and other variables.