From 1975 to 1999, Osterholm served in various roles at the Minnesota Department of Health (MDH), including as state epidemiologist and Chief of the Acute Disease Epidemiology Section from 1984 to 1999. At the MDH, Osterholm strengthened the department's role in infectious disease epidemiology, notably including numerous foodborne disease outbreaks, the association between tampons and toxic shock syndrome, and the transmission of hepatitis B and human immunodeficiency virus (HIV) in healthcare workers. Other work included studies regarding the epidemiology of infectious diseases in child-care settings, vaccine-preventable diseases (particularly "Haemophilus influenzae" type b and hepatitis B), Lyme disease, and other emerging and reemerging infections.