Professor Spitznagel has been a proponent of realistic, active data analysis in statistics for over thirty years. His first paper on the subject was given in 1971 at the Second Annual Conference on the Undergraduate Curriculum at Dartmouth College, while on his honeymoon.

He has worked extensively with medical school faculty in more than twenty different disciplines, including anesthesiology, cardiology, infectious diseases, oncology, ophthalmology, otolaryngology, and psychiatry. Over 100 of his 169 publications are indexed in The National Library of Medicine's indexing service ("Medline"). He has published in four of the five flagship English-language medical journals: NEJM, JAMA, Annals of Internal Medicine, and The Lancet. In addition, he has consulted extensively for such companies as MasterCard, Price Waterhouse, SmithKline Beecham, Anheuser-Busch, and Mallinckrodt.

These activities have led to numerous internship opportunities for his students, as well as in-depth teaching examples for his courses. Most recently he has used pharmacokinetics as the core around which to build Math 1323 Calculus II with Statistics. Each year he uses a different drug that is being tested for the generic market, and the students perform all the necessary pharmacokinetic and statistical computations needed for submission to the FDA Office of Generic Drugs.