Background Although the preferred route for transcatheter aortic valve replacement is through the femoral artery, alternatives remain necessary for patients with obstructive iliofemoral disease. Our valve team has developed a large experience using the carotid artery as a primary alternative vascular access approach for transcatheter aortic valve replacement (TAVR). We aim to compare short-term outcomes by access route in a single-center, high-volume, transcarotid (TC) TAVR program. Methods All patients undergoing TAVR between September 2012 and September 2018 were included in the study. Baseline demographics and outcomes were obtained from data our institution submitted in compliance with TVT (Transcatheter Valve Therapy) reporting and are supplemented by individual chart review. Results Overall, 1,153 commercial TAVR procedures were completed during the study period. Of these, 976 (85%) were transfemoral (TF), 105 (9%) were TC, and 72 (6%) were other (53 transapical, 14 transaxillary, 5 transaortic). TF patients had lower Society of Thoracic Surgeons (STS) scores (6.0% vs. 7.1% vs. 8.3%), peripheral vascular disease (24% vs. 88% vs. 72%), and cerebral vascular disease (11% vs. 17% vs. 32%) compared with TC and other patients, respectively (p \u3c 0.001). Combined in-hospital and 30-day mortality was 2.6% for the TF cohort versus 3.8% for TC (p = 0.36) and 13.9% for other (p \u3c 0.001). The stroke rate at 30 days was 3.7% for TF versus 3.8% for TC and 4.2% for other access routes (p = 0.98) (Table). Conclusion TAVR can be safely performed from the TC access route at a high-volume center with similar in-hospital and 30-day mortality and stroke rates compared with TF patients. Mortality was significantly increased, however, in patients treated with other alternative access routes