Under his tenure, MHS gained authorities to establish a national quarantine on sea and land (interstate), formal recognition of merit-based requirements for a Commissioned Corps of medical officers, and a new laboratory devoted to bacteriology, the newest public health science of the day.

Sanitary cordons, or quarantine, were the primary response to yellow fever, to block the progress of disease believed to be conveyed not only on boats and foot traffic but also now by railroad.

Advocates of a National Board of Health, including Army Surgeon John Shaw Billings, were spurred to action by the insufficient funding allotted to the Quarantine Act of 1878.

Over the following four years, Hamilton would press Billings at every turn, in a protracted, ultimately successful effort to regain authorities and recognition of MHS as the central Federal public health agency.

When Billings began publishing MHS's Bulletin under the Board's auspices, Hamilton countered by persuading Congress to fund new Marine Hospitals in locations like Sitka, Alaska, to strengthen collaboration with the Revenue Cutter Service (predecessor to the United States Coast Guard).

While the Board struggled with clumsy administrative mechanisms, Hamilton demonstrated how MHS's relationships with customs inspectors and the Revenue Cutter Service enabled a quick and effective quarantine response to smallpox aboard a Mississippi River steamboat at Fort Benton, Montana Territory (May 1882), and how MHS blocked yellow fever in Mexico from entry into Brownsville, Texas by means of a sanitary cordon hastily assembled around the region.

Although MHS would not receive formal authority to issue domestic quarantines until 1893, Hamilton and his staff worked with the Congress to advance incremental changes toward a national policy.

Hamilton made limited progress with the Congress realizing Woodworth's reform plans to set MHS on sound fiscal and professional moorings.

He was not able, however, to win an equal footing for MHS's Commissioned Corps with the salaries and ranks accorded to military medical officers and as a result, resigned his post as Surgeon General on June 1, 1891.