Background Adherence to evidence-based guidelines is an important quality indicator; yet, there is lack of assessment of adherence to performance measures in acute ischemic stroke for most world regions. Methods and Results We analyzed 19 604 patients with acute ischemic stroke in the China National Stroke Registry and 194 876 patients in the Get With The Guidelines--Stroke registry in the United States from June 2012 to January 2013. Compared with their US counterparts, Chinese patients were younger, had a lower prevalence of comorbidities, and had similar median, lower mean, and less variability in National Institutes of Health Stroke Scale (median 4 [25th percentile-75th percentile, 2-7], mean 5.4±5.6 versus median 4 [1-10], mean 6.8±7.7). Chinese patients were more likely to experience delays from last known well to hospital arrival (median 1318 [330-3209] versus 644 [142-2055] minutes), less likely to receive thrombolytic therapy (2.5% versus 8.1%), and more likely to experience treatment delays (door-to-needle time median 95 [72-112] versus 62 [49-85] minutes). Adherence to early and discharge antithrombotics, smoking cessation counseling, and dysphagia screening were relatively high (eg >80%) in both countries. Large gaps existed between China and the United States with regard to the administration of thrombolytics within 3 hours (18.3% versus 83.6%), door-to-needle time ≤60 minutes (14.6% versus 48.0%), deep venous thrombosis prophylaxis (65.0% versus 97.8%), anticoagulation for atrial fibrillation (21.0% versus 94.4%), lipid treatment (66.3% versus 95.8%), and rehabilitation assessment (58.8% versus 97.4%). Conclusions We found significant differences in clinical characteristics and gaps in adherence for certain performance measures between China and the United States. Additional efforts are needed for continued improvements in acute stroke care and secondary prevention in both nations, especially China.