Majerus, 64, has won more than 500 games as a college coach, including building a 95-69 record since taking over at St. Louis in 2007. The Billikens were 26-8 last season and advanced to the third round of the NCAA Tournament.
St. Louis University announced in August that Majerus would sit out this season due to health issues, with assistant coach Jim Crews guiding the team.
The school said Friday Majerus wouldn't return at all.
"Majerus continues to undergo evaluation and treatment in California for an ongoing serious heart condition," a release from the school said. "Majerus and his representatives have requested that SLU's Department of Athletics not provide any additional details regarding his health."
St. Louis Director of Athletics Chris May said "we think it is important to communicate, with transparency, to the student-athletes, staff and our loyal fans that Rick will not be returning."
Majerus coached previously at Marquette, Ball State and Utah -- taking the Utes to the NCAA title game in 1998. In 25 years of coaching, Majerus has a 517-215 record.