Perioperative acute ischemic stroke (AIS) is a feared complication of surgery that is associated with increased in-hospital mortality, length of hospital stay, disability, and discharge to long-term care facilities. This chapter presents a case study of a 70-year-old female with a past medical history of hypertension, hypercholesterolemia, myocardial infarction, and morbid obesity. Since treatment with intravenous tissue plasminogen activator (tPa) is contraindicated after major surgical procedures, the patient was taken to the interventional radiology suite and endovascular mechanical thrombolysis was performed. The main risk factors for perioperative stroke include (1) female sex, (2) advanced age, (3) atrial fibrillation, (4) cardiac valvular disease, (5) congestive heart failure, (6) history of previous transient ischemic attack (TIA) or stroke, (7) renal disease, (8) diabetes mellitus, (9) hypertension, and (10) general anesthesia. Preoperative evaluation of patients should focus on identifying and correcting potentially modifiable risk factors to reduce the risk of this devastating complication.