Background and Purpose-Antiphosphatidylserine antibodies (aPS) have been associated with the risk of ischemic stroke.However, it remains unclear whether aPS will influence clinical outcomes in patients with acute ischemic stroke. Methods-A total of 3013 patients with acute ischemic stroke recruited from 26 hospitals across China from August 2009 to May 2013 were included in the study The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes included death, major disability, recurrent stroke, and vascular events. Results-Composite outcome of death and major disability rates were 29.1% versus 23.9% in aPS-positive and aPS-negative groups. Compared with aPS-negative, adjusted odds ratios or hazard ratios (95% confidence interval) associated with aPS-positive were 1.35 (1.07-1.71), 1.63 (0.99-2.69), and 1.25 (0.98-1.59) for composite outcome of death or major disability, death, and major disability, respectively. For 1 interquartile range increase of aPS, the adjusted odds ratios or hazard ratios were 1.10 (1.01-1.20), 1.19 (1.05-1.35), and 1.05 (0.96-1.14), respectively. Adding aPS status to a model containing conventional risk factors improved risk prediction for composite outcome of death or major disability (net reclassification improvement index=11.3%, P=0.006; integrated discrimination improvement=0.2%, P=0.04). There was no significant association between aPS and risks of recurrent stroke and vascular events. Conclusions-We found that positive aPS increased risks of death or major disability at 3 months after an acute ischemic stroke, suggesting that aPS might be a prognostic marker for ischemic stroke.