Abstract Background The effect of saxagliptin on cardiovascular outcomes according to different hemoglobin A1c (HbA1c) levels has not been described. Thus, we analyzed the SAVOR-TIMI 53 trial to compare the cardiovascular effects of saxagliptin vs placebo according to baseline HbA1c. Methods A total of 16,492 patients with type 2 diabetes (HbA1c 6.5%-12.0% in the 6 months before randomization) and either a history of established cardiovascular disease or multiple risk factors for atherosclerosis were randomized to saxagliptin or placebo in addition to usual care. Patients were followed for a median of 2.1 years. The primary endpoint was cardiovascular death, myocardial infarction, or ischemic stroke. Results Patients were stratified by HbA1c at randomization into the following prespecified groups: <7%, 7%-<8%, 8%-<9%, and ≥9%. Baseline HbA1c ≥7% was associated with increased risk of cardiovascular death, myocardial infarction, or ischemic stroke (adjusted hazard ratio HRadj 1.35; 95% confidence interval CI, 1.17-1.58) but not hospitalization for heart failure (HRadj 1.09; 95% CI, 0.88-1.36). Saxagliptin neither increased nor decreased the risk of cardiovascular death, myocardial infarction, or ischemic stroke in patients with HbA1c <7% (HR 1.01; 95% CI, 0.78-1.31), 7%-<8% (HR 0.98; 95% CI, 0.80-1.20), 8%-<9% (HR 1.09; 95% CI, 0.85-1.39), ≥9% (HR 0.95; 95% CI, 0.77-1.18) ( P -interaction = .89). Conclusions Baseline HbA1c is associated with increased risk of macrovascular events but not hospitalization for heart failure. There was no heterogeneity in the effect of saxagliptin on cardiovascular events by baseline HbA1c, with cardiovascular death, myocardial infarction, or ischemic stroke neither increased nor decreased across the spectrum of baseline HbA1c values.