The presence of cholera during the winter, even if less severe, roused the Board of Health from its slumber, but the resulting implementation was half-hearted. Administrative resistance combined with the public's fear of proximity to the sick stymied the establishment of cholera hospitals. Only after the epidemic exploded in the spring was the city able to open hospitals in four public schools, despite protests that the buildings would forever be ruined and their future pupils tainted. But these hospitals were so poorly equipped and administered that cholera victims fought to avoid them, viewing time spent there as a virtual death sentence.

Dealing with the city's filth proved as great a problem as dealing with its sick. As the city thawed, the streets remained strewn with garbage. Political patronage rather than competence historically determined who aldermen hired to clean the streets; oversight of this work was minimal. Throughout the 1840s, the most reliable pickup crews had been the thousands of scavenging pigs that roamed the city. The pigs also contributed to the mess, however, and beginning in 1849 city reformers established a program to drive swine from the city (much to the chagrin of the laborers who slaughtered them for cheap meat). Although the Board of Health possessed the statutory power to compel aldermen to ensure the streets were cleaned, they didn't act, leading the local press to charge city leaders with criminal neglect. When the streets finally were cleaned by often unscrupulous private contractors, the task was done inefficiently: piles of filth remained on street corners for days before finally being removed for dumping into the rivers. Just as ineffective were the city's efforts to deal with the dead, many of whom were dumped into trenches on the northern outskirts of the city or doubled up in plots in local church cemeteries.

The Board of Health published updates on the progress of cholera, which only served to publicly record its own weakness. It was seemingly less active in 1849 than it had been during the earlier epidemic, suggesting that public health policy had failed to adapt to the city's growth. New York was now larger and dirtier, while corruption in the city's government was more widespread. Such a crisis seemed to call for increased governmental intervention in a time of crisis, but New Yorkers got the opposite from their city government.

By the time cholera had run its course in 1849, it had killed 5,071 New Yorkers. Forty percent of the dead were Irish immigrants. Cholera was a constant presence in the city through 1854, when the disease again reached epidemic proportions, killing 2,509. It then disappeared for a dozen years.