Ms Harris, 57, was in control for 85 minutes, while Mr Biden was placed under anaesthesia for a routine colonoscopy on Friday.
Mr Biden's doctor released a statement after the operation, saying he was healthy and able to execute his duties.
The medical examination came on the eve of the president's 79th birthday.
Ms Harris carried out her duties from her office in the West Wing of the White House, officials said.
She is the first woman - and the first black and South Asian American - to be elected US vice-president.
