On 6 October 1988, Pope John Paul II named him titular bishop of Populonia and consecrated him on 6 January 1989.

He was later named President of the Permanent Commission for the Care of the Historical and Artistic Monuments of the Holy See, serving from 8 March 2003 to 3 July 2009.

After the death of Cardinal Jan Pieter Schotte, Cardinal Marchisano was named on 5 February 2005 to succeed him as President of the Labour Office of the Apostolic See, retaining his other positions, while Archbishop Angelo Comastri was named to the unusual position of Coadjutor Archpriest of Saint Peter's and as Marchisano's successor Vicar General for the State of Vatican City, and President of the Fabric of Saint Peter.

[3] On 31 October 2006, Pope Benedict named Angelo Comastri to succeed Cardinal Marchisano as Archpriest of St Peter's Basilica.

[9][10] At the 28 June 2018 consistory, Pope Francis assigned the diaconate church of Santa Lucia del Gonfalone which Marchisano previously held to Aquilino Bocos Merino.