In 1864, a group of New York City physicians began to survey the sanitary conditions in the city. Their efforts inspired the Citizen's Association — a voluntary group of wealthy New Yorkers concerned with city governance — to form a Council of Hygiene and Public Health and underwrite a full survey of the city. Completed in 1865, the Report of the Citizens' Association of New York Upon the Sanitary Conditions of the City remains a landmark in the history of public health for its systematic approach towards studying the urban environment, and for its motivating principle that a city's moral and economic prosperity was intimately tied to its residents’ physical well-being. The report surveyed sanitary conditions ward by ward, and produced over three hundred pages of descriptions of just how decrepit much of the city was. The report solidified the link between sanitation and public health, and concluded that nothing short of a major overhaul of the city’s sanitary policies would avert recurrent crises.

With news of cholera's progress through Europe in 1865, and influenced by the popular 1865 sanitary report, the Common Council founded the Metropolitan Board of Health in February 1866. This board was larger, better organized, and possessed significantly more power than the previous one. Central to its activities were the physician-investigators who responded to individual complaints and monitored sanitation activity in the wards. By the end of March, the board was actively investigating health “nuisances.” By April, it had issued seven thousand orders to remove piled horse manure, rotting animal carcasses, and mountains of refuse. With the help of local police, the board forced residents to clean their yards, and tried to compel ward bosses to actually use the funds they had been given by the city to clean streets. Opposition was strong from both business owners hesitant to take on the expense of properly caring for their property and from local politicians anxious that a radical shift in their use of patronage would undermine their political power. The board spent significant time battling court injunctions brought in the spring by recalcitrant businessmen, and some of its efforts were stymied. Still, after two months of activity the city was much cleaner than it had been in years.

Cholera, however, was still to be dealt with. In April, as many New Yorkers expected, the first ships bearing cholera-infected passengers began to arrive in New York harbor. A quarantine station was set up on Staten Island, and all incoming ships were examined for infection. Cholera still managed to enter the city, with the first reported case on May 1. Unlike the two earlier outbreaks, this one occurred on 93rd Street, where wealthier New Yorkers tended to live. Two other cases followed within the week, one in the downtown Five Points neighborhood and another nearby. While New Yorkers prepared themselves for another dramatic surge in cholera cases, no more appeared until the first week of June. This delay could be attributed to the Board of Health, which dispatched sanitary crews with barrels of chloride and lime to each of the locales where the first victims took ill, boarded up their homes, and relocated the other residents to hospital tents for observation.

In June, more cases began to appear, almost entirely in the poorer and dirtier sections of the city. But the response of the Board of Health limited the disease’s spread. The board procured the Battery Army Barracks as a hospital, established storage spaces and distribution plans for disinfectants, and trained a small army of men in the methods of first response. Meanwhile, the board continued to investigate and cleanse “nuisances” throughout the city.

Despite these efforts, 1,137 New Yorkers died from cholera. Given the city’s growth since the previous epidemic, however, the death toll was significantly lower proportionally. As important as the lives saved was the progress marked by the city’s effectiveness in organizing a metropolitan response, and in embracing the role of protector of public health. New York’s Metropolitan Board of Health, largely as a result of its well-publicized response to cholera in 1866, offered a model for other American cities to follow in subsequent years.

New York would continue to face public health disasters in the nineteenth century and beyond. Influenza, diptheria, typhus, and tuberculosis were dealt with regularly, and concerns about disease accompanied each new wave of immigrants. Cholera itself continued to appear periodically later in the nineteenth century. After Robert Koch discovered the cholera vibrio in 1883, testing for the disease became much easier, and quarantine measures more effective. The last significant outbreak of cholera was in 1892, when 120 New Yorkers died. The Metropolitan Board of Health, building on the relative success of its response in 1866, grew in responsibility in the late-nineteenth century and continued advising on all sanitary matters in the city. Ultimately, its success contributed to the elevation of scientific responses to disease over moral and religious ones, and was one of the earliest and most successful progressive reforms.