The National Rifle Association issued a statement calling the defeated amendment "misguided."
"This amendment would have criminalized certain private transfers of firearms between honest citizens, requiring lifelong friends, neighbors and some family members to get federal government permission to exercise a fundamental right or face prosecution," NRA spokesman Chris Cox said in a statement.
"As we have noted previously, expanding background checks, at gun shows or elsewhere, will not reduce violent crime or keep our kids safe in their schools," he said.
New York Mayor Michael Bloomberg, however, issued an angry statement on behalf of Mayors Against Illegal Guns.
"Today's vote is a damning indictment of the stranglehold that special interests have on Washington," the group's statement said. "More than 40 U.S. senators would rather turn their backs on the 90 percent of Americans who support comprehensive background checks than buck the increasingly extremist wing of the gun lobby."
Gov. Dan Malloy of Connecticut, which has passed some of the strictest gun laws in America in the past month, questioned why senators would vote against a measure he believed to be very popular with the public.
"There is much more that needs to be done on the issue of gun violence prevention. But when the Senate cannot come together on an issue that is supported by the vast majority of Americans, there is little to no hope that common sense will prevail," Malloy said in a statement. "The members who voted against this proposal should be ashamed of themselves."
Shortly after the vote, the Progressive Change Campaign Committee announced it would launch an ad campaign targeting Democratic senators who voted against the bill. Those included Mark Pryor, D-Ariz., Mark Begich, D-Alaska, Max Baucus, D-Mont. and Heidi Heitkamp, D-N.D.
Earlier today Manchin told ABC News that regardless of the vote's outcome, the need to impose new gun measures "would not go away."
ABC News' Mary Bruce contributed to this report.