Brian Sack, head of the markets group at the Federal Reserve Bank of New York, will step down in June.
Sack managed, among other assets, mortgage-backed securities and Treasurys purchased by the Fed as part of its monetary policy, such as Operation Twist and QE2.
He was not involved in the sell of Maiden Lane assets the Fed acquired as part of the American International Group (AIG) bailout.
Sack joined the NY Fed in June 2009. He will be placed on leave, separated from access from bank information until September.
"Brian's service to the bank over the past three years has been critical to our response to the financial crisis and the country's economic recovery," said NY Fed CEO William Dudley. "I accepted his resignation with great regret and wish him well."