Mr Biden, 78, drove early on Friday to the medical centre in the Washington suburbs for his first routine physical exam as president.
Press secretary Jen Psaki said he would be under anaesthesia during the procedure and would transfer power to Ms Harris.
She later posted a new tweet saying that the US president was in "good spirits" and resumed his duties at around 11:35 in the morning.
As Ms Psaki pointed out earlier on Friday, in 2002 and 2007, Vice-President Dick Cheney assumed the role of temporary president when George Bush had colonoscopies.
Ms Harris, 57, who is the first woman - and the first black and South Asian American - to be elected US vice-president, temporarily took control of the US military and nuclear weapons.
Mr Biden had his last full exam in December 2019, when doctors found the former vice president to be “healthy, vigorous” and “fit to successfully execute the duties of the Presidency,” according to a doctor’s report at the time.
Mr Biden is the oldest person to serve as president, and interest in his health has been high since he declared his candidacy for the White House in 2019.
Dr Kevin O’Connor, who has been Biden’s primary care physician since 2009, wrote in a three-page note that the then-presidential candidate was in overall good shape.
In that report, Dr O’Connor said that since 2003, Mr Biden has had episodes of atrial fibrillation, a type of irregular heartbeat that is potentially serious but treatable.
At the time, Dr O’Connor cited a list of tests that showed Biden’s heart was functioning normally and his only needed care was a blood thinner to prevent the most worrisome risk, blood clots or stroke.
Mr Biden had a brush with death in 1988, requiring surgery to repair two brain aneurysms, weak bulges in arteries, with one of them leaking.
Mr Biden has never had a recurrence, his doctor said, citing a test in 2014 that examined his arteries.
When Mr Biden took office he brought Dr O’Connor back to the White House to continue serving as his doctor, and O’Connor was expected to lead a team of experts in conducting Mr Biden’s physical exam.
Once the Covid-19 pandemic emerged in early 2020, Biden’s team took intense steps to keep the then-candidate and now-president healthy as the virus raged and took a disproportionate toll among older populations.
Mr Biden received his first dose of the Covid-19 vaccines in December 2020 and his second dose just two weeks before taking office.
He received a booster dose in late September.