She is a public advocate for the inclusion of women in clinical trials and is frequently cited in New York's annual "Top Doctors" issue.

[5] She has authored several books, including Why Men Die First: How to Lengthen Your Lifespan; Eve's Rib: The New Science of Gender-Specific Medicine and How It Can Save Your Life; The Female Heart: The Truth About Women and Coronary Artery Disease; and Why Men Never Remember and Women Never Forget, which have been translated into multiple languages.

[6][7] Additionally, she edited the medical textbook Principles of Gender-Specific Medicine, which addresses sex-specific aspects of normal human function and disease.

M. Irené Ferrer facilitated Legato's education at New York University College of Medicine and covered her tuition expenses.

In 1968, Legato assumed the role of instructor in medicine, marking the beginning of her academic career at Columbia University College of Physicians and Surgeons.

Legato has received the Martha Lyon Slater Fellowship from 1965 to 1968 and the J. Murray Steele Award in 1971, both granted by the New York Heart Association.

She has served on study sections to evaluate NIH grant applications at the National Heart, Lung, and Blood Institute.

From 1995 to 1998, she served as a charter member of the advisory board to the newly established Office of Research in Women's Health at the NIH.

During that time, she co-chaired the task force responsible for setting the research agenda on women's health for the 21st century.

The Ladies' Home Journal established the annual Marianne J. Legato Award in Gender-Specific Medicine in her honor in 2006.