AbstractObjectivesTo identify the major complications independently associated with unfavorable outcomes in right‐sided large hemisphere infarction (RLHI) patients.MethodsWe retrospectively enrolled consecutive patients admitted within 24 h with the diagnosis of RLHI. The unfavorable outcome was defined as a modified Rankin Scale score of 4–6 at 3 months. Univariate and multivariate analyses were performed to identify the major complications independently associated with 3‐month unfavorable outcomes.ResultsOf the 171 cases with RLHI included, 126 (73.7%) had unfavorable outcomes at 3 months: A total of 64 (37.4%) cases died, and 62 (36.3%) lived with severe disability. Stroke‐related complications occurred in 168 (98.2%) patients during hospitalization. The five most common stroke‐related complications were pulmonary infection (75.4%), electrolyte disorder (61.4%), hypoalbuminemia (49.1%), malignant brain edema (MBE) (48.5%), and hemorrhagic transformation (48.0%). RLHI patients with unfavorable outcomes had more frequent MBE (58.7% vs. 21.4%,p< .001), pulmonary infection (86.5% vs. 42.9%,p< .001), gastrointestinal bleeding (46.8% vs. 28.6%,p= .038), electrolyte disorder (68.3% vs. 40.5%,p= .001), acute renal failure (32.5% vs. 4.8%,p< .001), and hypoalbuminemia (61.1% vs. 11.9%,p< .001) than patients with favorable outcome. Multivariate analyses suggested that only MBE (adjusted OR 4.06, 95% confidence interval [CI] 1.14–14.48,p= .031), pulmonary infection (adjusted OR 4.69, 95%CI 1.48–14.85,p= .009), and hypoalbuminemia (adjusted OR 6.58, 95%CI 1.74–24.86,p= .005) were independently associated with 3‐month unfavorable outcome in patients with RLHI.ConclusionsMost of the RLHI patients have at least one stroke‐related complication during hospitalization, and nearly three‐quarters suffered unfavorable outcomes. Only MBE, pulmonary infection, and hypoalbuminemia are independently associated with 3‐month unfavorable outcome.