Background and Purpose— Many patients are transferred to comprehensive stroke centers for advanced acute ischemic stroke care, especially after intravenous tissue plasminogen activator. We sought to determine differences in the baseline characteristics and outcomes between patients with acute ischemic stroke presenting directly to our academic stroke center’s front door versus transfers-in from another acute care hospital. Methods— Using our institutional Get With The Guidelines (GWTG)-Stroke registry, we analyzed all 3660 consecutively admitted patients with acute ischemic stroke (January 2005–June 2012). Univariate and multivariable models explored differences in front door versus transfer-in patients. Results— Fifty percent of all patients with acute ischemic stroke were transfer-in. Compared with front door patients, transfer-in were younger (67±16 versus 71±15 years; P <0.001), had worse median initial National Institutes of Health Stroke Scale score (7.0 versus 4.0; P <0.001), more often had limb weakness (35% versus 27%; P <0.001) or aphasia (16% versus 11%; P <0.001), and received intravenous tissue plasminogen activator (29% versus 13%; P <0.001). Despite a trend toward higher in-hospital mortality in transfer-in patients, the difference was not statistically significant (13% versus 11%; P =0.08) between the 2 groups. Transfer-in patients had a longer hospital length of stay (5 versus 4 days; P <0.001) and were more often discharged to inpatient rehabilitation (48% versus 34%; P <0.001). Independent predictors of in-hospital mortality were increasing age (odds ratio [OR], 1.38 per decade [1.23–1.55]; P <0.001), atrial fibrillation (OR, 1.47 [1.12–1.93]; P =0.006), coronary artery disease (OR, 2.02 [1.53–2.67]; P <0.001), and initial National Institutes of Health Stroke Scale (OR, 1.20 per point [1.18–1.23]; P <0.001). Transfer status was not independently associated with in-hospital mortality (OR, 0.99 [0.76–1.29]; P =0.928). Conclusions— Despite having more severe strokes on arrival at our hospital, transfer-in patients had similar in-hospital mortality versus front door patients and were more likely to be discharged to rehabilitation. These outcomes lend support to the concept of regionalized stroke care and concentrating patients who are more disabled at more advanced stroke care centers.