"She's eager to get back to the office," Reines said in a statement, adding that the secretary and her family are grateful for the excellent care she received at New York-Presbyterian Hospital.
Reines said details of when Clinton will return to work will be clarified in the coming days.
Clinton had been in the hospital since Sunday, when doctors discovered the clot on an MRI test during a follow-up exam stemming from a concussion she suffered earlier in December. While at home battling a stomach virus, Clinton had fainted, fallen and struck her head, a spokesman said.
"Grateful my Mom discharged from the hospital and is heading home," the secretary's daughter, Chelsea, wrote on Twitter. "Even more grateful her medical team (is) confident she'll make a full recovery."
Earlier Wednesday, the State Department said Clinton had been speaking by telephone with staff in Washington and reviewing paperwork while in the hospital.
"She's been quite active on the phone with all of us," said State Department spokeswoman Victoria Nuland.
Before being released from the hospital, Clinton was photographed Wednesday getting into a black van with her husband, Bill, Chelsea and a security contingent to be taken elsewhere on the sprawling hospital campus. The last time Clinton had been seen publicly was on Dec. 7.
Clinton's physicians had said Monday that there was no neurological damage but that they planned to keep her in the hospital while they established the proper dose for the blood thinners. They said Clinton, 65, had been in good spirits and was engaging with doctors, family and aides.
Sidelined by her illness for most of December, Clinton was absent on Dec. 21 when President Barack Obama nominated Sen. John Kerry, D-Mass., to succeed her when she steps down at the start of Obama's second term, as had long been planned. The illness also forced to cancel scheduled testimony before Congress about a scathing report into the attack on the U.S. diplomatic mission in Benghazi, Libya, that killed four Americans, although she could still testify in the future.
"She has said that she is open" to going before Congress, Nuland said Wednesday, while Clinton was still hospitalized. "We are working with them now on their schedule, because there's also a question of when they are going to be in."
Clinton had expected to return to work this week and had already started to resume regular phone contact with her foreign counterparts. On Saturday, the day before the clot was discovered, Clinton had a half-hour conversation with Lakhdar Brahimi, the U.N. envoy to Syria, in which the two discussed the state of affairs in that country, her spokeswoman said.
Also on Saturday, Clinton spoke by telephone with Qatari Prime Minister and Foreign Minister Hamad bin Jassim Al Thani, discussing recent developments in Syria, Afghanistan and the Palestinian territories.
The illness has also raised questions about Clinton's political future and how her health might influence her decision about whether to run for president in 2016, as prominent Democrats have been urging her to consider.
Clinton suffered from a blood clot in 1998, midway through her husband's second term as president, although that clot was located in her knee.