[7] Guinan began her career working in a Chiclet gum factory developing flavors after graduating with a chemistry degree from Hunter College.

Shortly after joining the company, she encountered her first glass ceiling: male colleagues were making far higher salaries than their female counterparts.

In this time, she heavily considered pursuing a career in space-related endeavors as US space programs blossomed, but again faced obstacles.

[8] After completing her medical residency, Guinan joined a two-year training program with the Epidemic Intelligence Service of the CDC,[9] and asked to work with the World Health Organization (WHO) on smallpox eradication.

[8] She threatened to write a letter to the prime minister, Indira Gandhi, who was a female herself, directly addressing the alleged ban.

Guinan spent five months with a team in Uttar Pradesh, India, where she worked to identify locals suffering from smallpox and subsequently ring vaccinate those susceptible to the disease in the immediate area (generally a 10-mile radius from the infected individual).

[8] Reflecting on her career in medicine, Guinan stated, "I grew up with parents who were immigrants from Ireland, and they always told me that I was in the greatest country in the world and that I should be giving back what I was given.

In 1995–98, still with the CDC, she was the named the Chief of the Urban Research centers (New York, Seattle, Detroit), a community-based prevention and health promotion effort.

Not the least of these are the medical detectives who collect clues, analyze data, investigate suspected cases, and carry out their public health mission".

In 2016, Guinan published an autobiography entitled Adventures of a Female Medical Detective: In Pursuit of Smallpox and AIDS, which was co-written by Anne D. Mather.