Background and Objectives:To explore regional discrepancy of the adherence to guideline-recommended stroke interventions, with respect to the stroke belt division (north vs. south), the economic development division (east vs. middle vs. west), and potential interaction.Methods:We conducted a retrospective observational study using data from the Chinese Stroke Center Alliance (CSCA) from August 2015 to August 2019. The primary outcome was hospital personnel adherence to eleven individual guideline-recommended treatments. The co-primary outcomes included two summary measures: a composite score (range, 0 [nonadherence] to 1[perfect adherence]), and an all-or-none binary outcome for adherence to evidence-based stroke. Regional disparities were assessed according to the stroke belt division and the economic development division respectively, as well as the interaction between these two divisions. Multivariate regression models with generalized estimating equations were used to analyze the outcomes.Results:This study included 838,229 patients with acute ischemic stroke (AIS) from 1,473 hospitals. The overall quality of care in the non-belt regions (southern China) was higher than the stroke-belt regions (northern China), as reflected by a higher composite score (0.77vs 0.75; adjusted OR: 1.03 [95% CI, 1.02-1.04]; P < 0.001) and a higher all-or-none measure (25.5% vs 22.0%; 1.32 [1.17-1.49], P < 0.001). Patients in the East and the Central had higher odds of using intravenous tissue-type plasminogen activator (East: 1.81 [95% CI, 1.51-2.18], P < 0.001; Central: 1.57 [95% CI, 1.26-1.95], P < 0.001), early antithrombotics (East: 1.77 [1.49-2.11], P < 0.001; Central: 1.37 [1.12-1.66], P < 0.001), lipid-lowering medications (East: 1.29 [1.08-1.53], P < 0.001), and DVT prophylaxis (East: 1.28 [1.08-1.50], P = 0.003) compared to those in the West. Patients in the non-belt regions had higher odds of getting dysphagia screening (1.82 [1.55-2.13], P < 0.001) and rehabilitation assessment (which though varied among different economic development levels). Reflected by significant interaction effects, for patients in the East, those in the non-belt regions had greater odds of receiving anticoagulation (1.62 [1.34-1.96]; P < 0.001) but lower odds of receiving antihtrombotics (0.63 [0.52-0.77]; P < 0.001) and antidiabetic medication (0.87 [0.77-0.99]; P= 0.03); for patients in the West, those in the non-belt regions were less likely to receive antihypertensive (0.64 [0.46-0.88]; P = 0.004) and antidiabetic (0.66 [0.54-0.81]; P < 0.001) medications.Discussion:Stroke care performance measures differed across regions, along the stroke-belt division, and the economic development division. The overall quality of care in the non-stroke-belt regions was higher than the stroke-belt regions. The two divisions had interaction effects on several individual measures.