[7] In August 2008, Genoa purchased half of the registration rights of Ranocchia for €1.55 million[8] and sent him on loan to Bari, rejoining Arezzo coach Conte, where he won the Serie B Championship, obtaining promotion to Serie A the following season, and forming a promising defensive partnership with fellow emerging Italian centre-back Leonardo Bonucci.

After a link with Inter Milan in February 2010, the clubs agreed a deal in June 2010 which involved the transfer of young striker Mattia Destro.

[27] In the 2017–18 season, under guidance of Luciano Spalletti, Ranocchia was once again used rarely, making only 13 appearances between league and cup, scoring twice in the process.

[36] However, he was given an opportunity to start on 20 February 2020, during which he made his 200th Inter appearance in all competitions by captaining the team in a 2–0 win at Ludogorets Razgrad in the first leg of the round of 32 of the Europa League.

[37][38] During the 2020–21 season, Ranocchia won his first scudetto with Inter; although he did not make many appearances for the club, he took on a crucial leadership role for the team within the dressing room.

[51] Ranocchia has been described as a large, strong, aggressive, and physically imposing centre back, with good tactical knowledge and concentration, as well as an ability to read the game and time his tackles well.

[57] A former attacking midfielder,[58] he was also known for being comfortable in possession due to his solid technique and reliable distribution, which allowed to him to play the ball out from the back or carry it out from the defence; these qualities initially led him to be compared to Alessandro Nesta in the Italian media, a player whom he admired.

[52][53][55][56][59] He was capable of playing in any position in a three–man defence, or as part of a central defensive partnership in a four–man back-line, although he was more suited to the former system; he was also occasionally used as a full-back on either side of the pitch.

[52][63] In February 2019, Inter manager Luciano Spalletti praised his leadership, stating: "Ranocchia is the real captain because he is the one who speaks often, whose messages on social media everyone gets.

He is the leader that is in the squad but you don’t notice him, but during the difficult times steps out and says what needs to be said.”[64][65] Despite his reputation as a generally reliable defender,[66] in later seasons, Ranocchia did, however, draw criticism due to his decision making, inconsistency, and proneness to errors when under pressure, as well as his lack of pace, while his fitness was also affected by several injuries.

[74][75][76] He had also initially played as a forward in his youth, due to his speed, technique, and height, before being shifted further back as he grew physically with age.