"Unemployment is still above 7.2 percent, our gross domestic product, the measure of our economy's performance, is still sluggish with 2.5 percent economic growth in 2010 and only 2.8 percent now," he said. "That's not the kind of improvement we expected from the Fed's program."
Manchin is not alone in his criticism of the program.
Even some Federal Reserve regional bank presidents say it hasn't produced the desired results.
During a Nov. 1 interview on CNBC, Philadelphia Fed President Charles Plosser said the Fed should have begun tapering its asset purchase policy earlier this year.
"I have not been a particular fan of QE," Plosser said. "I don't think it's terribly effective."
Dallas Fed President Richard Fisher said during a speech at a banking conference in Australia earlier this month that Congressional brinksmanship over U.S. tax and budgetary policies canceled out much of the effect that should have come from quantitative easing.
"While the Fed has been moving at the speed of a boomer in full run, the federal government of the United States has at best exhibited the adaptive alacrity of a koala (without being anywhere near as cute)," Fisher said.
Manchin said he felt the Fed's continued purchase of Treasury bonds would allow Congress to keep on delaying any substantive fiscal reform in coming years.
"I believe that the current lending policy of the Fed will continue to allow Congress to run up record debts and deficits while our economy continues to lag behind," he said.
While Manchin is opposing Yellen's nomination, its highly likely President Barack Obama's nominee will end up becoming the first woman to lead the central bank. She would also be the first Democrat to fill the post since Paul Volcker left the position in 1986.
Yellen's path to confirmation also became easier on Thursday when the full Senate voted to change its rules for approving all presidential nominees other than Supreme Court selections. Now a simple majority will be required, instead of 60 votes.
Republicans could still try to delay the final vote to focus attention on other issues. For example, Sen. Lindsey Graham has threatened to hold up nominations for government positions until survivors of last year's deadly attack on the diplomatic post in Benghazi, Libya, appear before Congress.
But Democrats control 55 votes in the chamber, so such tactics could easily be overcome.
The Associated Press contributed to this report.
Contact writer Jared Hunt at busin...@dailymail.com or 304-348-4836.