Professor Rothwell is a clinical neurologist with an interest in stroke. He was appointed as Clinical Lecturer in Oxford in 1996, was awarded an MRC Senior Clinical Fellowship in 2000, and was given the title of Professor of Clinical Neurology at the University of Oxford in 2004. He founded the Stroke Prevention Research Unit in 2000, which has since published over 250 scientific papers.

In addition to prevention of stroke, his research interests include hypertension, the risks and benefits of aspirin, and the more general theme of how best to apply the results of clinical trials and other forms of research to clinical decisions with individual patients in routine clinical practice.