He was admitted to Gemelli Hospital mid-week with breathing difficulties, and later diagnosed with bronchitis.
The Vatican had said he was responding to antibiotics and would be released on Saturday, depending on test results.
"I wasn't frightened, I'm still alive," the 86-year-old pontiff told reporters and tearful well wishers outside the hospital before being driven away.
He was seen smiling and waving from the car, before getting out to speak to a crowd. He then headed for the Vatican.
The Pope's admission to hospital came ahead of the busiest week in the Christian calendar to mark Easter.
Holy Week, as it is known, includes a busy schedule of events and services that can be physically demanding.
Vatican spokesman Matteo Bruni said on Friday that the Pope was excepted to take part in this weekend's service for Palm Sunday.
The Argentine pontiff, who marked 10 years as head of the Catholic Church earlier this month, has suffered a number of health issues throughout his life, including having part of one of his lungs removed at age 21.
He has also used a wheelchair in recent months because of problems related to his knee.
But the Pope has remained active, visiting the Democratic Republic of Congo and South Sudan in February. The previous month, he led the funeral of his predecessor Pope Benedict XVI.