Bush spokesman Jim McGrath says the wife of former President George H.W. Bush was released from Houston Methodist Hospital late Saturday morning.
The 88-year-old has been hospitalized since Monday.
The spokesman said the Bush family matriarch responded well to medication and "she's great." He had no other immediate details on her condition or future treatment.
She and her husband, the 41st president, live in Houston. The nation's longest-married presidential first couple will celebrate their 69th wedding anniversary Monday.
Barbara Bush had heart surgery in March 2009 for a severe narrowing of the main heart valve. She also was hospitalized in November 2008 for a perforated ulcer. In 2010, she was admitted to the hospital after having a mild relapse of Graves disease, a thyroid condition for which she was treated in 1989.
Her 89-year-old husband spent nearly two months in the same hospital and was discharged in January 2013 after treatment for a bronchitis-related cough and other health issues.
Their son, George W. Bush, served as the 43rd U.S. president.
The Associated Press contributed to this report.