Objective- Serum Dkk-1 (dickkopf-1) level has been shown to be elevated in patients with ischemic stroke, but its impact on clinical outcomes of ischemic stroke remains unclear. The aim of this study is to investigate the association between serum Dkk-1 and prognosis of ischemic stroke. Approach and Results- We measured serum Dkk-1 levels in 3178 patients with ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was a combination of all-cause mortality and major disability (modified Rankin scale score, >= 3) at 1 year after stroke. Secondary outcomes were stroke recurrence and vascular events. After multivariate adjustment, elevated Dkk-1 levels were associated with an increased risk of primary outcome (odds ratio, 1.40; 95% CI, 1.03-1.89; P-trend=0.015) when 2 extreme quartiles were compared. Each SD increase of log-transformed Dkk-1 was associated with 12% (95% CI, 1%-24%) increased risk of primary outcome. Multiple-adjusted spline regression model showed a linear association between serum Dkk-1 and risk of primary outcome (P for linearity, 0.039). Subgroup analyses further confirmed these associations. The addition of serum Dkk-1 to conventional risk factors improved the predictive power for primary outcome (net reclassification improvement: 10.11%, P=0.029; integrated discrimination improvement: 0.21%, P=0.028). Conclusions- High serum Dkk-1 levels at baseline were associated with poor prognosis at 1 year after ischemic stroke, suggesting that serum Dkk-1 may be a potential prognostic biomarker for ischemic stroke. Further studies from other samples of patients with ischemic stroke are needed to replicate our findings and to clarify the potential mechanisms.