He was promoted to Surgeon the following year, and served successively in the marine hospitals at St. Louis, Cincinnati, Baltimore, and New York City.

While he was in charge of the marine hospital in Staten Island, New York, the Hygienic Laboratory (forerunner of the National Institutes of Health) was established there in 1887 by Supervising Surgeon General John B. Hamilton.

Under Wyman's administration, the Laboratory significantly increased its research activities, including studies on diseases such as hookworm and Rocky Mountain spotted fever, and was provided with a new building in 1901.

In the early years of the twentieth century, Surgeon General Wyman found himself in the midst of a controversy over the San Francisco plague of 1900–1904.

The service first became involved in the situation in 1900 when MHS physician Joseph J. Kinyoun, stationed in San Francisco, confirmed by bacteriological analysis that the death of a laborer in the city's Chinatown section was due to bubonic plague.

By 1903, however, the situation had become serious enough that an emergency conference was held in Washington, D.C., and a recommendation was made that all traffic between California and the rest of the country be halted unless Federal authorities were permitted to carry out their eradication campaign.

The service under Wyman also cooperated with state and local health authorities in the control of other infectious diseases such as yellow fever.

He also played a leading role in the first four Inter-American Sanitary Conferences, acting as President of the first two and attending the next two as the United States Delegate.