In 1993 it was modified for the first time: the track length was increased to 4.060 km (2.523 mi), with the possibility to race both the long and the old short loop; moreover, new facilities and new pit garages were built.

It was at Misano during the 1993 Italian Grand Prix that the defending 500 cc World Champion Wayne Rainey's career ended after he fell and suffered a broken spine.

The first MotoGP race held on the circuit after the modifications was the 2007 San Marino and Rimini Coast Grand Prix, which was won by "home" marque Ducati.

During the 2010 Moto2 event, Japanese rider Shoya Tomizawa was killed after losing control of his bike and being subsequently struck by both Scott Redding and Alex de Angelis.

On 3 November 2011, the circuit owners announced that it would be named after Marco Simoncelli, an Italian motorcycle racer who died during the 2011 Malaysian Grand Prix in Sepang a week prior.