Born in Lograto (Province of Brescia), over the course of his career Maifredi has managed at several clubs such as Bologna, Brescia and others, though he is most noted for his short spell with Juventus, where he lost six games in a row and got sacked. His footballing approach has been famously named as calcio champagne (champagne wine football) due to both his prominent attacking style of play and as a reference to his former professional career as a wine representative.
In 2005, Maifredi was on course to sign with Lazio, but its supporters were not keen on Maifredi's appointment, and demonstrated against it, which forced club president Claudio Lotito to back down and appoint Giuseppe Papadopulo instead.
On 24 September 2013, Maifredi returned on the bench for a spare game, co-training with assistant coach Fabio Micarelli after head coach Marco Giampaolo failed to report for three days. The next day, Brescia appointed Maifredi as new head coach, thus ending a 13-year absence of his from head coaching roles into football. His period as a manager was however only on a caretaker basis, as he left after only one game - a 0–2 loss to Latina - to leave room for new boss Cristiano Bergodi.