Background: The platelet-to-lymphocyte ratio (PLR) is an inflammation marker of acute ischemic stroke, but its significance in patients with hemorrhage transformation (HT) after acute ischemic stroke with large-artery atherosclerosis (AIS-LAA) is unclear, and we also identified the relationship between PLR and in-hospital mortality of HT after AIS-LAA. Methods: This was a retrospective analysis of patients with AIS-LAA. The PLR was calculated according to platelet and lymphocyte counts on admission. HT was defined on follow-up magnetic resonance imaging or computed tomography when neurologic deterioration worsened during hospitalization. The univariate analysis and multivariate logistic regression were per-formed to assess the association of PLR, HT and in-hospital mortality of HT after AIS-LAA. Results: We included 328 Chinese AIS-LAA patients (mean age 67.2 +/- 11.1 years; 70.4% male). HT occurred in 38 patients (11.6%). After multivariate regression analyses, NRL (odds ratio [OR] 1.354, 95% confidence interval [CI] 1.176-1.559, P<0.001) and PLR (odds ratio [OR] 3.869, 95% confidence interval [CI] 2.233-5.702, P<0.001) were independently associated with HT after AIS-LAA. The area under the ROC curve (AUC) value of PLR (0.72, 95% CI (0.64-0.80), P<0.001) tested a greater discriminatory ability compared with neutrophil-lymphocyte ratio (NLR) (0.67, 95% CI (0.58-0.76), P<0.001). Meanwhile, PLR was found to be significantly related to HT after AIS-LAA, including in subtypes of artery-to-artery embolization (aOR 1.699, 95% CI 1.298-3.215, P<0.001), in-situ thrombosis (aOR4.499, 95% CI 1.344-9.054, P<0.001) and branch atheromatous disease (aOR3.239, 95% CI 1.098-8.354, P<0.001). Increased PLR predicts high in-hospital mortality of HT after AIS-LAA (OR 1.041, 95% CI (1.006-1.077), P=0.020; aOR 1.053, 95% CI (1.004- 1.104), P=0.034). Conclusion: High PLR is associated with greater risk of HT in AIS-LAA patients, including in artery-to-artery embolization, in-situ thrombosis and branch atheromatous disease. Meanwhile, increased PLR predicts high in-hospital mortality of HT after AIS-LAA.