Prabhakaran moved to Chicago in 2006 and accepted a research position at Rush University Medical Center. As a neurologist at Rush, Prabhakaran focused on stroke prevention and treatment. In this role, he helped identify three bedside clinical features to assist physicians in accurately diagnosing transient ischemic attacks from disorders that might mimic their symptoms. He eventually left Rush to become a neurologist at Northwestern Memorial Hospital and an associate professor of neurology at the Northwestern University Feinberg School of Medicine. At Northwestern, Prabhakaran became the principal investigator for the National Institutes of Health's (NIH) Chicago Stroke Trials Consortium to support clinical trials for stroke prevention, treatment and recovery. In this role, he helped influence public policy change in Chicago in regards to emergency care in Chicago’s stroke centers. His research team published findings that found that suspected stroke patients had a higher chance of survival if they were transported to the nearest primary stroke center instead of the nearest emergency room.
