Milan have won both Serie A meetings this season and are unbeaten in nine games against their counterparts from the capital; however, the Giallorossi have a recent track record of going the distance in Europe.
Match preview
Having seen off Rennes after dropping down from the Champions League, in which they finished third in the so-called 'Group of Death', Milan swept aside Slavia Prague in the last 16, cruising to a 7-3 aggregate success by comfortably winning both legs.
That continued an impressive spell of form for the seven-time European champions, who last week tightened their grip on second place in Serie A by beating Lecce 3-0, thereby posting seven straight wins for the first time since 2006.
Milan have now scored at least once in their last 29 matches across all competitions, notching three goals in three of their last four, and their front line has certainly clicked into gear following a sticky patch during mid-winter.
No fewer than four members of Stefano Pioli's squad have reached double figures for the season: Olivier Giroud (15) and Christian Pulisic (13) join Rafael Leao (12) and Ruben Loftus-Cheek (10), the latter of whom scored in both legs of the win over Slavia.
It is the first time so many players have scored 10 times or more for the Rossoneri in 15 years, and there can be few doubts that they possess sufficient firepower to challenge on two fronts over the concluding part of this season.
While city rivals Inter Milan seem to have the Scudetto wrapped up, leading by 14 points with just seven games left to play, Pioli's men will still want to beat Juventus to finish runners-up and, more importantly, win the club's first Europa League.
Proving particularly tough to beat on home turf, Milan's record of 11 wins and just two losses from 15 Serie A contests is an impressive one, and they are on a 10-match streak without defeat at San Siro ahead of Roma's arrival.
While Milan reached the Champions League semis last season, before suffering a painful exit to Inter, Roma's recent runs to two UEFA finals have captured the imagination in Italy's Eternal City.
Having beaten Feyenoord to win the inaugural Europa Conference League in 2022, last year's loss to Sevilla in the Europa League decider was hard to take, and the latter result perhaps signalled the beginning of the end for former boss Jose Mourinho.
Under new coach Daniele De Rossi, who is back at his beloved club until the end of the season, Roma have proved a different proposition to the team beaten by Milan and arch-rivals Lazio at the bitter end of Mourinho's reign, having since lost just twice in 15 games.
There have been some 10 wins to celebrate following De Rossi's return, including Saturday's Derby della Capitale revenge mission against Lazio, which was decided by Gianluca Mancini's first-half goal.
Now occupying fifth place in the Serie A standings, Roma are eyeing Champions League football for next term, though they could alternatively secure a seat at Europe's top table by winning the Europa League final in Dublin.
They may have unexpectedly crushed Brighton and Hove Albion in the last 16, but the Giallorossi have won only two of their last 14 away matches in continental competition, with no wins from their last eight in the knockout phase.
Furthermore, the club that lost an all-Italian UEFA Cup final to Inter back in 1991 have recently struggled to beat Thursday's hosts: Roma have won just one of their last 13 meetings with Milan - including a 3-1 defeat at San Siro in January - and they are on their worst winless run against the Rossoneri for over 40 years.
AC Milan Europa League form:
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AC Milan form (all competitions):
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Roma Europa League form:
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Roma form (all competitions):
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Team News
Milan will be without first-choice defender Fikayo Tomori on Thursday evening, as he serves a UEFA suspension, while Tommaso Pobega and Pierre Kalulu are both unavailable due to injury.
Stefano Pioli will have Ruben Loftus-Cheek back in the fold, though, after he missed Saturday's win over Lecce because of a one-match ban. The in-form Englishman has been directly involved in 11 goals in his 15 previous Europa League appearances, netting four from four this season.
German centre-back Malick Thiaw has returned to training, so should battle it out with ex-Roma player Simon Kjaer to partner Matteo Gabbia at the heart of the hosts' four-man defence.
Meanwhile, Roma are missing Sardar Azmoun and Evan Ndicka due to injury and suspension respectively, while neither Dean Huijsen or Rasmus Kristensen were included on the club's squad list for the knockout stages.
Either Chris Smalling or Marcos Llorente should replace Ndicka in the visitors' defence, while Daniele De Rossi can call upon plenty of experience up front.
Joining Paulo Dybala and Romelu Lukaku in a potent attacking trio, ex-Milan forward Stephan El Shaarawy has five assists in nine Europa League appearances this season.
Back at San Siro, where he so often represented Inter with distinction, Lukaku has been involved in 11 goals in his last eight away games in the competition. The Belgian striker scored in all of his first five meetings with Milan but has since failed to find the net in any of his last five.
AC Milan possible starting lineup:
Maignan; Calabria, Kjaer, Gabbia, Hernandez; Adli, Reijnders; Pulisic, Loftus-Cheek, Leao; Giroud
Roma possible starting lineup:
Svilar; Celik, Mancini, Llorente, Angelino; Cristante, Paredes, Pellegrini; Dybala, Lukaku, El Shaarawy